universidad complutense de madrid · ejemplo el perro. el segundo estudio incluido en este trabajo...

UNIVERSIDAD COMPLUTENSE DE MADRID

Facultad de Veterinaria

TESIS DOCTORAL

Feline degenerative joint disease: studies of prevalence, etiology and diagnosis

Enfermedad degenerativa articular felina: estudios de prevalencia,

etiología y diagnóstico

MEMORIA PARA OPTAR AL GRADO DE DOCTOR

PRESENTADA POR

Milagros Freire González

Director

B. Duncan X. Lascelles

Madrid, 2014

© Milagros Freire González, 2014

1

Universidad Complutense de Madrid


Feline Degenerative Joint Disease: Studies of

prevalence, etiology and diagnosis

by


Thesis submitted at the Complutense University of Madrid

Thesis Director

Dr. B Duncan X Lascelles

2014

3

Universidad Complutense de Madrid


Enfermedad Degenerativa Articular Felina:

estudios de prevalencia, etiología y diagnóstico

Memoria para optar al grado de doctor

presentada por


Director de Tesis

Dr. B Duncan X Lascelles

2014

7

INDICE

9

Página

AGRADECIMIENTOS 11

RESUMEN 13

SUMMARY 23

INTRODUCTION 31

OBJECTIVES 37

PUBLICATIONS 41

Publication 1: Lascelles BD, Henry JB 3rd, Brown J, Robertson I, Sumrell

AT, Simpson W, Wheeler S, Hansen BD, Zamprogno H, Freire M, Pease A.B.

Cross-sectional study of the prevalence of radiographic degenerative joint

disease in domesticated cats. Veterinary Surgery. 2010;39(5):535-44. 45

Publication 2: Freire M, Robertson I, Bondell HD, Brown J, Hash J, Pease

AP, Lascelles BD. Radiographic evaluation of feline appendicular degenerative

joint disease versus macroscopic appearance of articular cartilage. Veterinary

Radiology & Ultrasound. 2011;52(3):239-47. 57

Publication 3: Freire M, Brown J, Robertson ID, Pease AP, Hash J, Hunter S,

Simpson W, Thomson Sumrell A, Lascelles BD. Meniscal Mineralization

Domestic Cats. Veterinary Surgery. 2010;39(5):545-52. 69

Publication 4: Freire M, Meuten D, Lascelles BD. Histopathology of articular

cartilage and synovial membrane from elbow joints with and without

degenerative joint disease in domestic cats. Veterinary Pathology. 2014 Jan 29.

[Epub ahead of print]. 79

DISCUSSION 95

CONCLUSIONS 107

REFERENCES 113

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Lascelles%20BD%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Henry%20JB%203rd%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Brown%20J%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Robertson%20I%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Sumrell%20AT%5BAuthor%5D&cauthor=true&cauthor_uid=20561321


http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Simpson%20W%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Wheeler%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Hansen%20BD%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Zamprogno%20H%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Freire%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20561321

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Pease%20A%5BAuthor%5D&cauthor=true&cauthor_uid=20561321



http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Bondell%20HD%5BAuthor%5D&cauthor=true&cauthor_uid=21418370


http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Hash%20J%5BAuthor%5D&cauthor=true&cauthor_uid=21418370

http://www.ncbi.nlm.nih.gov.prox.lib.ncsu.edu/pubmed?term=Pease%20AP%5BAuthor%5D&cauthor=true&cauthor_uid=21418370



http://www.ncbi.nlm.nih.gov/pubmed/24476939

11

AGRADECIMIENTOS

A veces las cosas son inexplicablemente imposibles hasta que alguien altruistamente te tiende la

mano que hace que todo el esfuerzo y trabajo realizado se materialice y cobre sentido. No

agradezco a los que no me pusieron impedimentos sino a los que creyeron que este trabajo era

posible y me ayudaron a que se hiciera realidad.

Gracias, Javier Benito de la Víbora.

Gracias, Ignacio Álvarez Gómez de Segura.

Dedicado a Miriam Martín García.

13

rESUMEN

15

La tesis detallada en este documento está dividida en cuatro secciones que corresponden

con artículos publicados en diferentes revistas de difusión veterinaria. En conjunto estos estudios

tienen como objetivo general profundizar en el mejor conocimiento de la patología articular en

gatos domésticos, en concreto, avanzar en los conocimientos acerca de la prevalencia, etiología y

diagnóstico de esta enfermedad.

El primer estudio incluido en esta tesis se diseñó para determinar la prevalencia de la

presencia de signos radiológicos indicativos de enfermedad articular degenerativa en una

población de gatos seleccionados aleatoriamente. El estudio fue diseñado como un estudio

prospectivo observacional. Los animales incluidos fueron 100 gatos domésticos con dueño,

seleccionados de la base de datos de una clínica veterinaria felina local, y fueron equitativamente

distribuidos en cuatro grupos de edades (0-5, 5-10, 10-15 y de 15 a 20 años de edad). Estos

animales fueron seleccionados aleatoriamente de la base de datos (independientemente de su

estado de salud en el momento de la realización del estudio) y durante su visita al hospital fueron

sedados para realizar el estudio radiológico de todas las articulaciones apendiculares y la

columna vertebral. La información generada se analizó por medio de un test de regresión Quasi-

Poisson para investigar la relación entre los datos demográficos de la población, los valores de la

analítica sanguínea (hematológicos y bioquímicos) análisis de orina y la severidad de la

enfermedad degenerativa articular presente. Los resultados más destacables fueron que la

mayoría de los gatos (92%) presentaron evidencia radiológica de enfermedad articular

degenerativa; el 91% presentaban al menos una articulación apendicular afectada de enfermedad

articular degenerativa y el 55% presentaba una o más regiones de la columna vertebral con

signos radiológicos indicativos de esta enfermedad. Las articulaciones apendiculares más

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frecuentemente afectadas de enfermedad articular degenerativa, ordenadas de mayor a menor

frecuencia, fueron la cadera, rodilla, tarso y codo. El segmento torácico de la columna vertebral

fue el que más frecuentemente presentaba signos radiológicos indicativos de degeneración

articular. Muchas variables presentaron una asociación significativa con la presencia de

enfermedad degenerativa articular, pero cuando estas variables fueron agrupadas para el análisis,

la única asociación estadísticamente significativa encontrada fue entre edad y enfermedad

degenerativa articular (P < 0,0001). Por cada año de aumento de edad de los gatos, el valor total

del grado de enfermedad articular degenerativa esperado aumenta en un porcentaje estimado en

13,6% (95% intervalo de confianza: 10,6%, 16,8%). Este estudio permitió por primera vez de

una forma prospectiva, con un número elevado de animales y realizando radiografías de todas las

articulaciones apendiculares y segmentos vertebrales, establecer que la presencia de signos

radiológicos indicativos de enfermedad articular degenerativa tiene una prevalencia muy alta en

gatos domésticos, incluso en animales jóvenes, y está fuertemente asociada con la edad del

animal. Aún son necesarios futuros estudios para determinar las consecuencias clínicas de esta

enfermedad en gatos domésticos.

Gracias a estudios de prevalencia como el mencionado arriba y otros publicados

recientemente, la enfermedad articular degenerativa ha sido descrita como una de las

afectaciones más comunes en los gatos domésticos pero durante mucho tiempo no ha estado

claro cuáles son los signos radiológicos indicativos de esta enfermedad en la especie felina, o si

estos signos radiológicos son diferentes a otras especies en las que si están bien descritos, por

ejemplo el perro. El segundo estudio incluido en este trabajo consistió en describir como los

signos radiológicos considerados indicativos de la presencia de enfermedad articular

17

degenerativa se relacionan con la degeneración del cartílago articular de las articulaciones

apendiculares en esta especie. Treinta gatos adultos, eutanasiados por causas independientes a la

realización de este estudio, fueron evaluados. Signos radiológicos indicativos de la presencia de

enfermedad articular degenerativa se evaluaron en radiografías ortogonales de las articulaciones

del codo, tarso, rodilla y cadera. Estas mismas articulaciones se inspeccionaron visualmente

postmortem con el objetivo de detectar la presencia de lesiones indicativas de enfermedad

degenerativa articular, y determinar el grado de lesión del cartílago articular usando la escala

“Grado de Daño Articular Total” (Total Cartilage Damage Score). Los resultados más

significativos de este estudio fueron que evaluando todas las articulaciones en conjunto hay una

correlación que, aunque significativa, es baja entre el grado de daño articular observado durante

la inspección visual de las articulaciones y la severidad de osteofitos y mineralizaciones de los

tejidos blandos asociados con tejidos articulares detectados radiográficamente, así como con el

grado de enfermedad articular degenerativa asignado a las radiografías de cada articulación

subjetivamente (subjective radiographic DJD score). Evaluando cada articulación por separado,

la mayoría de las correlaciones estudiadas fueron estadísticamente significativas, sin embargo el

grado de correlación fue superior a 0,4 (moderado) únicamente en las articulaciones del codo y la

cadera para las correlaciones entre la presencia de osteofitos en las radiografías y el grado

subjetivo radiológico de enfermedad degenerativa articular con el daño del cartílago articular

detectado macroscópicamente. Las articulaciones en las que es más probable encontrar daño del

cartílago articular sin presentar ningún signo radiológico indicativo de enfermedad degenerativa

articular son la rodilla (71% de las rodillas radiológicamente normales presentaron daño del

cartílago articular), seguido de la articulación de la cadera (57%), el codo (57%) y la articulación

del tarso (46%). Los resultados de este estudio determinan que los signos radiológicos presentes

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en las articulaciones apendiculares en gatos domésticos no se correlacionan con la presencia de

daño en el cartílago articular, el número de articulaciones con daño articular que no presentaron

ningún signo radiológico de enfermedad articular degenerativa es alto, y otras modalidades de

diagnóstico por imagen deberían ser consideradas como opciones para el diagnóstico de la

enfermedad articular degenerativa felina.

La evaluación de las radiografías durante el desarrollo de los dos estudios anteriores,

puso de manifiesto la presencia de mineralizaciones en la articulación de la rodilla en un número

importante de animales y esto propició el planteamiento de un estudio en el que los objetivos

principales fueron determinar la prevalencia de mineralizaciones del menisco detectables

radiográficamente en gatos domésticos y evaluar la asociación entre la mineralización del

menisco y la presencia de enfermedad articular degenerativa en la articulación de la rodilla. El

estudio fue diseñado como un estudio observacional prospectivo en el que se evaluaron 100

gatos con dueño y 30 gatos adultos que fueron eutanasiados por motivos no relacionados con

este estudio. Los 100 gatos con dueño evaluados, fueron seleccionados aleatoriamente de una

base de datos perteneciente a una clínica veterinaria felina local, y la información recopilada de

estos animales se utilizó para determinar la prevalencia de la mineralización del menisco. Las

articulaciones de la rodilla de los gatos eutanasiados fueron utilizadas para evaluar la relación

entre la presencia y el tamaño de la mineralización del menisco (usando radiografías de gran

resolución), la presencia de signos radiológicos indicativos de enfermedad degenerativa articular

y la presencia de lesiones en el cartílago articular. Los meniscos extraídos de estas articulaciones

fueron procesados y evaluados histológicamente. Los resultados más significativos de este

estudio fueron que el 46% de los 100 gatos evaluados tenían evidencia radiológica de

19

mineralización del menisco en una o las dos rodillas. El grado de dolor detectado en el examen

ortopédico en las rodillas no presentó diferencias significativas entre articulaciones con y sin

mineralización del menisco (P = 0,38). Treinta y cuatro de las 57 rodillas evaluadas postmortem

presentaban mineralización del menisco, y esta mineralización estaba localizada en el cuerno

craneal del menisco medial en todos los casos. El porcentaje del área total del menisco que

presentaba mineralización se correlacionó significativamente con el grado de lesión del cartílago

articular del cóndilo medial del fémur (r2

= 0,6; P < 0,0001) y del cóndilo medial de la tibia (r2

=

0,5; P < 0,0001) así como con el grado de lesión global del cartílago articular de la articulación

(r2

= 0,36; P < 0,0001) y la severidad de los signos radiológicos de enfermedad articular

degenerativa presentes (r2

= 0,8; P < 0,0001). En conclusión, la mineralización del menisco es

una condición presente comúnmente en gatos domésticos y parece indicar la presencia de

enfermedad degenerativa articular en el compartimento medial de la articulación de la rodilla en

esta especie.

Finalmente debido a que la articulación del codo en los gatos domésticos ha sido descrita

en numerosos estudios como una de las articulaciones apendiculares más comúnmente y

severamente afectadas por enfermedad articular degenerativa, un cuarto estudio fue diseñado

para evaluar las lesiones macroscópicas e histológicas en la articulación del codo en 30 gatos

adultos, inmediatamente después de la eutanasia. Lesiones macroscópicas indicativas de

enfermedad degenerativa articular se encontraron en 22 de los 30 gatos evaluados (39 codos)

(73,33% de los gatos; 65% de las articulaciones estudiadas) y las lesiones del cartílago variaron

desde ligera erosión superficial a destrucción completa del cartílago articular con exposición del

hueso subcondral. La distribución de las lesiones en el cartílago se corresponde con la presencia

20

de enfermedad degenerativa del compartimento medial de la articulación (las lesiones más

severas se localizaron en el proceso coronoideo medial de la ulna y en el epicóndilo medial del

húmero). En 10 codos se encontraron fragmentos osteocondrales intra-articulares, en algunos

casos libres en el espacio articular y en otros adheridos a la membrana sinovial. En general el

grado de inflamación de la membrana sinovial fue solo ligero incluso en casos con lesiones

severas del cartílago articular, y presentó una correlación baja con el grado de destrucción del

cartílago articular detectado macroscópicamente. No se encontró evidencia macroscópica o

histológica de la presencia de fragmentación del proceso coronoideo medial de la ulna en ningún

caso, ni siquiera en aquellos que presentaron fragmentos osteocondrales intra-articulares. Las

lesiones observadas en los animales estudiados probablemente representan osteocondromatosis

sinovial secundaria a la presencia de enfermedad articular degenerativa. La patogénesis de la

compartimentalización medial de la enfermedad degenerativa articular en los gatos estudiados no

ha podido ser determinada pero no parece estar relacionada con la presencia de fragmentación

del proceso coronoideo medial u osteocondritis disecante del húmero.

Con estos resultados, creemos que los estudios detallados en esta tesis han contribuido a

mejorar el conocimiento de las características radiológicas y patológicas de la enfermedad

degenerativa articular felina. Algunos de los signos radiológicos que se pueden encontrar

comúnmente en esta especie, como la mineralización del menisco de la articulación de la rodilla

han sido finalmente detallados y han sido asociados con un daño severo del cartílago articular.

Los estudios de etiología realizados han permitido determinar, por ejemplo, que algunas causas

muy bien descritas y conocidas en otras especies domesticas causantes de enfermedad

degenerativa en el codo, como es el caso de la displasia de codo en la especie canina, hayan sido

21

descartadas como causas de enfermedad degenerativa en esta misma articulación en gatos

domésticos. Muchas preguntas están aún sin responder y futuros estudios son necesarios para

elucidar más aspectos relacionados con la etiología y la significación clínica de esta enfermedad

en los gatos domésticos.

23

sUMMARY

25

The detailed herein thesis is divided into four sections that correspond to manuscripts

published in different journals of veterinary diffusion. Together these studies’ general aim is to

deepen the knowledge of joint disease in domestic cats, in particular, improve what we know

about the prevalence, etiology, and diagnosis of this disease.

The first study described this thesis was designed to determine the prevalence of

radiographic signs of degenerative joint disease (DJD) in a randomly selected sample of

domestic cats. The study was designed as a prospective observational study. One hundred client-

owned cats from a single feline only veterinary practice and equally distributed across 4 age

groups (0-5, 5-10, 10-15, and 15-20 years old) were randomly selected (regardless of health

status) and sedated for orthogonal radiographic projections of all joints and the spine. Quasi-

Poisson regression analysis was used to investigate the relationship between patient

demographics, blood biochemistry, hematologic and urine analysis variables, and DJD severity.

The most significant results were that the majority of cats (92%) had radiographic evidence of

DJD; 91% of animals had at least one site of appendicular DJD and 55% had one or more sites of

the axial column affected with DJD. Affected joints in descending order of frequency were hip,

stifle, tarsus and elbow. The thoracic segment of the spine was more frequently affected than the

lumbosacral segment. Although many variables were significantly associated with DJD, when

variables were combined, only the association between age and DJD was significant (P < .0001).

For each 1-year increase in cat age, the expected total DJD score increases by an estimated

13.6% (95% confidence interval: 10.6%, 16.8%). This study allowed for the first time in a

prospective manner and with a high number of animals, to determine that radiographically

visible DJD is very common in domesticated cats, even in young animals and that is strongly

26

associated with age however it is necessary further investigation to determine the clinical

consequences of this disease.

As a consequence of studies of prevalence as the one described above and others more

recently published, degenerative joint disease is now described as one of the most common

conditions affecting domesticated cats; however for many years, it was not clear which were the

radiographic signs indicative of this disease in feline species or if these radiographic signs were

different to other species in which they are accurately described, for example in canine species.

The second study included in this thesis was designed to describe the relationship between the

radiographic signs considered indicative of the presence of degenerative joint disease and the

macroscopic cartilage degeneration in appendicular joints in cats. Thirty adult cats euthanized for

reasons unrelated to this study were evaluated. Orthogonal digital radiographs of the elbow,

tarsus, stifle and coxofemoral joints were evaluated for the presence of DJD. The same joints

were dissected for visual inspection of changes indicative of DJD and macroscopic cartilage

damage was graded using a Total Cartilage Damage Score. The most significant results were that

when considering all joints, there was statistically significant fair correlation between cartilage

damage and the presence of osteophytes and joint-associated mineralizations, and the subjective

radiographic DJD score. Most correlations were statistically significant when looking at the

different joints individually, but only the correlation between the presence of osteophytes and the

subjective radiographic DJD score with the presence of cartilage damage in the elbow and

coxofemoral joints had a value above 0.4 (moderate correlation). The joints most likely to have

cartilage damage without radiographic evidence of DJD are the stifle (71% of radiographically

normal joints), followed by the coxofemoral joint (57%), elbow (57%), and tarsal joint (46%).

27

The results of this study support that radiographic signs of appendicular joints do not relate well

with articular cartilage degeneration, and that other modalities should be evaluated to aid in

making a diagnosis of feline DJD.

The evaluation of radiographs of appendicular joints of domestic cats during the

development of the two previous studies, revealed the presence of mineralizations in the stifle

joint in a large number of animals and this encouraged the development of the next study. The

main objectives were to determine the prevalence of radiographically detectable meniscal

mineralization in domestic cats and assessment of the association between meniscal

mineralization and the presence of degenerative joint disease in the stifle joint in this species.

The study was designed as a prospective study. Thirty adult cats euthanized for reasons unrelated

to this study and 100 client-owned domestic cats were evaluated. The client-owned cats were

randomly selected from a database of a feline-only single practice and the information from these

animals was used to determine the prevalence of radiographic signs indicative of meniscal

mineralization. Stifle joints from feline cadavers were used to evaluate the relationship between

the presence and size of meniscal mineralization (using high-resolution X-ray), radiographic

DJD, and cartilage damage. Menisci were also harvested and processed for histological

evaluation. The most significant results of this study were that 46% of the client-owned cats had

meniscal mineralization detected in 1 or both stifles. Pain scores were not significantly different

between stifle with meniscal mineralization and those with no radiographic pathology (P = .38).

Thirty-four of 57 cadaver stifles had meniscal mineralization, which was always located in the

cranial horn of the medial meniscus. Percentage mineralization of the menisci was significantly

correlated with the cartilage damage score of the medial femoral (r2 = 0.6; P < .0001) and tibial

28

(r2

= 0.5; P < .0001) condyles as well as with the total joint cartilage damage score (r2

= 0.36; P <

.0001) and DJD score (r2

= 0.8; P < .0001). In conclusion, meniscal mineralization is a common

condition in domestic cats and seems to indicate medial compartment DJD of the stifle joint. The

clinical significance of this condition in feline species is uncertain and further work is needed to

determine if the meniscal mineralization is a cause or a consequence of joint degeneration.

Finally because the elbow joint in domestic cats has been described in numerous studies

as one of the appendicular joints most commonly and severely affected by DJD, a fourth study

was designed to evaluate the pathologic changes present in the elbow joints of 30 adult cats

immediately following euthanasia. All the joints were carefully opened for macroscopic

evaluation of the articular cartilage and samples of joint capsule and articular cartilage of ulna,

humerus and radius were processed for histological evaluation. Macroscopic evidence of

degenerative joint disease was found in 22 of 30 cats (39 elbow joints), (73.33% cats; 65% elbow

joints), and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of

the hyaline cartilage with exposure of the subchondral bone. Distribution of the lesions in the

cartilage indicated the presence of medial compartment joint disease (with the most severe

lesions located in the medial coronoid process of the ulna and medial humeral epicondyle).

Synovitis scores were mild overall and correlated only weakly with macroscopic cartilage

damage. Intra-articular osteochondral fragments either free or attached to the synovium were

found in 10 joints. Macroscopic or histologic evidence of fragmented coronoid process was not

found even in those cases with intra-articular osteochondral fragments. Lesions observed in these

animals are most consistent with synovial osteochondromatosis secondary to degenerative joint

disease. The pathogenesis for the medial compartmentalization of these lesions has not been

29

established, but a fragmented medial coronoid process or osteochondritis dissecans does not

appear to play a role.

Together these studies have contributed to improve the knowledge of radiographic,

macroscopic and pathologic characteristics of joint disease in domestic cats. Some of the

radiographic signs present in this species, such as mineralization of the medial meniscus of the

stifle joint, have been found to be associated with a severe damage of the articular cartilage.

Etiology studies conducted have allowed to determine, for example, that very well described and

known causes of joint pathology in other species, such as elbow dysplasia in dogs, have been

dismissed as causes of degenerative disease in the same joint in domestic cats. Many questions

are still unanswered and future studies are needed to further elucidate aspects of the etiology and

clinical significance of DJD in domestic cats.

31

INTRODUCTION

33

Until very recently, little was known about feline degenerative joint disease (DJD). Only a few

retrospective studies were available a few years ago,1-4

and although they stressed the high prevalence of

radiographic signs of DJD in this species, there were still many unknown aspects regarding this condition

in cats. Over the years, there has been much speculation on feline DJD and likely, many erroneous

presumptions based on DJD in other species. It seems timely to critically review what is now known

about feline DJD and to identify needed information to appropriately address this clinical entity. This

work embraces different studies that were conducted to deepen the knowledge of prevalence, etiology and

diagnosis of feline DJD.

Several studies have been performed to evaluate the prevalence of feline DJD. Beadman et al 5

undertook the first extensive radiographic evaluation of DJD of the feline axial skeleton. Since then, the

studies that have been carried out suggest that the most frequent site of axial skeleton DJD is the area T7-

10.6, 7,8

The most severe lesions appear to be in the lumbar or lumbo-sacral region. The incidence of axial

skeleton DJD is markedly different between the different studies, likely reflecting an increase in

frequency of axial skeleton DJD with age. The available information at the time of publication of our

study of the prevalence of feline DJD (publication number 1, Page x), suggested that the appendicular

joints most commonly affected by DJD are the hip and elbow, followed by stifle or possibly tarsus.6-12

Although these studies suggested a high incidence of radiographic signs indicative of appendicular and

axial DJD in cats, prior to publication of the study of prevalence included in this thesis, no studies had

been published that evaluate every appendicular joint and every region of the axial skeleton, in a

randomly selected population of cats to ascertain the prevalence of appendicular and axial DJD in this

species. For more information please refer to manuscript number 1 of this document (Lascelles

BD, Henry JB 3rd, Brown J, Robertson I, Sumrell AT, Simpson W, Wheeler S, Hansen BD, Zamprogno

H, Freire M, Pease A.B. Cross-sectional study of the prevalence of radiographic degenerative joint

disease in domesticated cats. Veterinary Surgery. 2010;39(5):535-44).














34

The high prevalence of this disease generated interest in describing the clinical signs, evaluating

causes and predisposing factors and measuring the pain associated with the radiographic changes. Despite

this interest, for many years there was no information on how the radiographic findings of feline DJD

related to actual degeneration of various joint components, such as cartilage. Seemingly, there were no

studies in cats comparing the radiographic appearance of joints with histological findings. Such

comparison was necessary to improve radiographic interpretation and to address the idea that feline DJD

may be associated with different radiographic signs and macroscopic lesions compared with other species,

as it has been previously suggested. For more information please refer to manuscript number 2 of this

document (Freire M, Robertson I, Bondell HD, Brown J, Hash J, Pease AP, Lascelles BD. Radiographic

evaluation of feline appendicular degenerative joint disease versus macroscopic appearance of articular

cartilage. Veterinary Radiology & Ultrasound. 2011;52(3):239-47).

Although common causes of OA in cats have been outlined before,13

there is little documented

supporting evidence and most studies evaluating prevalence speculate on the cause of DJD. Clarke et al 8

indicated that about 25% of OA cases resulted from trauma, with more than 50% of cases having no

obvious cause suggesting that they may have been primary OA. Hardie et al 9 found little evidence in

medical records to indicate likely cause of DJD and postulated that observed OA/DJD was likely

secondary to undetermined factors (eg. elbow dysplasia, chronic low-grade trauma, subtle

malarticulation). Several authors have suggested that a large proportion of DJD in cats is primary;

however there is currently no supporting evidence. It is possible that unrecognized factors, such as those

that play a role in other species, may be responsible for DJD in cats. It is also possible that as yet

unrecognized factors that do not play a significant role in DJD in other species, such as systemic

inflammatory disease, may predispose to, or be the cause of, DJD in the cat. Documented secondary

causes of DJD in cats are nutritional, hip dysplasia and noninfectious polyarthropathies and infectious

arthropathies.








35

Of interest is the frequent bilateral occurrence of feline DJD, a characteristic of DJD caused by

bilateral congenital malformations (eg. joint dysplasia, osteochondrosis), systemic factors (eg.

endocrinopathy, metabolic disorders), neurogenic factors, chronic overuse or possible primary OA. Joints

reported to be most commonly affected by DJD are hip and stifle14

or shoulder and elbow15

depending of

the study and bilateral occurrence is most common in coxofemoral, carpal, elbow and stifle joints.14

We

evaluated the presence of meniscal mineralization in domestic cats as a possible cause of bilateral DJD in

the stifle joint. Meniscal mineralization is a poorly understood condition that has been reported in reptiles,

rodents, birds, non-domestic cats, and non-human primates.16-19

Although described in people, it is

considered a rare condition20-27

and there have been a few case reports in dogs and domestic cats.26, 28, 29

The cause of meniscal mineralization is unknown. It had been suggested that meniscal mineralization is a

normal anatomic feature in non-domestic cats,17

a primary vestigial anomaly in dogs and cats,16, 29

and to

occur secondary to trauma or in association with cranial cruciate ligament rupture in dogs and cats.16, 28

At

the time of publication of our study of meniscal mineralizations in domestic cats, the frequency of

occurrence of this condition was unknown. It was also unknown if meniscal mineralization was

associated with joint pain or lameness or if meniscal mineralization was associated with degeneration of

joint tissues such as cartilage. For more information please refer to manuscript number 3 of this document

(Freire M, Brown J, Robertson ID, Pease AP, Hash J, Hunter S, Simpson W, Thomson Sumrell A,

Lascelles BD. Meniscal Mineralization Domestic Cats. Veterinary Surgery. 2010;39(5):545-52).

The elbow joint in cats has been described as one of the joints most commonly affected by DJD with

an incidence of radiographic evidence of DJD in approximately 41% of the cases and bilateral disease

reported in 28% of the cases.30 The elbow joint is commonly affected by DJD in dogs as well,31 but

unlike cats the majority of canine patients with elbow joint DJD have known underlying predisposing

factors such as fragmented medial coronoid process (FMCP) or osteochondritis dissecans (OCD). To

date, these forms of elbow dysplasia have not been proven to be present in cats. One report suggested the

36

occurrence of elbow dysplasia (fragmented medial coronoid process) as a cause of elbow disease in a

feline patient after removal of several osteochondral fragments from both elbow joints.32

As part of the

study presented in this thesis as publication number 2, we have observed similar fragments in cats with

elbow DJD, in which evidence of macroscopic cartilage damage is present but with apparently intact

coronoid processes of the ulna on macroscopic examination. Even though the prevalence of radiographic

signs of DJD in the elbow joint in cats is high and fragmented medial coronoid process has been

suggested to be present in this species, the etiology of feline elbow DJD is unknown and the presence of

feline elbow dysplasia has not been confirmed. The last study included in this work was designed to

report the histological characteristics of the articular surfaces, synovial membranes and intra-articular

osteochondral fragments in elbow joints from cats with and without DJD and compare the findings with

those reported to be present in dogs with FMCP. For more information please refer to manuscript number

4 (Freire M, Meuten D, Lascelles, BDX. Pathology of articular cartilage and synovial membrane from

elbow joints with and without degenerative joint disease in domestic cats. Veterinary Pathology. 2014 Jan

29. [Epub ahead of print]).


37

OBJECTIVES

39

Study 1: Cross-Sectional study of the Prevalence of Radiographic Degenerative Joint disease in

Domesticated Cats. Veterinary Surgery. 2010; 39(5):535-544.

a. Evaluate the prevalence of radiographic signs of DJD in a sample of cats selected at

random from a population of domestic cats.

b. Evaluate associations between severity of radiographic DJD and patients demographics,

serum biochemical profile, hematological profile and urinalysis profile variables.

Study 2: Radiographic evaluation of feline appendicular degenerative joint disease versus macroscopic

appearance of articular cartilage. Veterinary Radiology & Ultrasound. 2011;52(3):239-47.

a. Evaluation of the sensitivity of digital and analog radiographs for detection of

radiographic signs indicative of DJD in cats.

b. Evaluate the association between radiographic features of DJD and the presence of

macroscopically detectable articular cartilage damage in feline appendicular joints.

Study 3: Meniscal Mineralization Domestic Cats. Veterinary Surgery. 2010;39(5):545-52.

a. Determine the prevalence of radiographically detectable meniscal mineralization in

domestic cats.

b. Determine the association between meniscal mineralization and the presence of stifle

joint DJD as indicated by cartilage damage.

40

Study 4: Histopathology of articular cartilage and synovial membrane from elbow joints with and

without degenerative joint disease in domestic cats. Veterinary Pathology. 2014 Jan 29. [Epub ahead of

print].

a. Evaluate the histological characteristics of the articular surfaces, synovial membranes

and intra-articular osteochondral fragments in elbow joints from cats with and without

DJD.

b. Compare histological findings of elbow joints of cats with DJD with those published for

dogs with fragmented medial coronoid process.

c. Evaluate the association between macroscopic and histological degree of damage of

articular surfaces with the degree of synovial inflammation and hyperplasia.


41

PUBLICATIONS

43

Publication 1

Lascelles BD, Henry JB 3rd, Brown J, Robertson I, Sumrell AT, Simpson W, Wheeler

S, Hansen BD, Zamprogno H, Freire M, Pease A.B. Cross-sectional study of the prevalence of

radiographic degenerative joint disease in domesticated cats. Veterinary Surgery.

2010;39(5):535-44.

Publication 2

Freire M, Robertson I, Bondell HD, Brown J, Hash J, Pease AP, Lascelles BD. Radiographic

evaluation of feline appendicular degenerative joint disease versus macroscopic appearance of

articular cartilage. Veterinary Radiology & Ultrasound. 2011;52(3):239-47.

Publication 3

Freire M, Brown J, Robertson ID, Pease AP, Hash J, Hunter S, Simpson W, Thomson Sumrell

A, Lascelles BD. Meniscal Mineralization Domestic Cats. Veterinary Surgery. 2010;39(5):545-

52.

Publication 4

Freire M, Meuten D, Lascelles BD. Histopathology of articular cartilage and synovial

membrane from elbow joints with and without degenerative joint disease in domestic cats.

Veterinary Pathology. 2014 Jan 29. [Epub ahead of print].





















45

PUBLICATION 1

Cross-sectional study of the prevalence of radiographic degenerative joint disease

in domesticated cats. Lascelles BD, Henry JB 3rd

, Brown J, Robertson I, Sumrell

AT, Simpson W, Wheeler S, Hansen BD, Zamprogno H, Freire M, Pease A.B.

Veterinary Surgery. 2010;39(5):535-44.















Cross-Sectional Study of the Prevalence of RadiographicDegenerative Joint Disease in Domesticated Cats

B. Duncan X. Lascelles1 BVSc, PhD, DSAS(ST), Diplomate ACVS & ECVS, John B. Henry2 III PhD,James Brown3 DVM, MS, Diplomate ACVR, Ian Robertson3 BVSc Diplomate ACVR,Andrea Thomson Sumrell1 RVT, Wendy Simpson4 DVM, Simon Wheeler1,5 BVSc, PhD,Bernie D. Hansen1 DVM, Diplomate ACVECC & ACVIM, Helia Zamprogno1 DVM, PhD,Mila Freire1 DVM, and Anthony Pease3 DVM, MS, Diplomate ACVR1Comparative Pain Research Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 2Statistics Department, North

Carolina State University, Raleigh, NC, 3Diagnostic Imaging, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 4Morrisville

Cat Hospital, Morrisville, NC and 5Novartis, Basal, Switzerland

Corresponding Author

B.D.X. Lascelles, Comparative Pain

Research Laboratory, Department of

Clinical Sciences, College of Veterinary

Medicine, North Carolina State University,

Raleigh, NC 27606

E-mail: [email protected]

Submitted July 2009

Accepted November 2009

DOI:10.1111/j.1532-950X.2010.00708.x

Objective: To determine the prevalence of radiographic signs of degenerative jointdisease (DJD) in a randomly selected sample of domestic cats.Study Design: Prospective observational study.Animals: Client-owned cats.Methods: Cats (n=100) from a single practice and equally distributed across4 age groups (0–5; 5–10; 10–15, and 15–20 years old) were randomly selected (re-gardless of heath status) and sedated for orthogonal radiographic projections ofall joints and the spine. Quasi-Poisson regression analysis was used to investigatethe relationship between patient demographics, blood biochemistry, hematologicand urine analysis variables, and DJD severity.Results: Most (92%) cats had radiographic evidence of DJD; 91% had at least1 site of appendicular DJD and 55% had Z1 site of axial column DJD. Affectedjoints in descending order of frequency were hip, stifle, tarsus, and elbow. Thethoracic segment of the spine was more frequently affected than the lumbosacralsegment. Although many variables were significantly associated with DJD, whenvariables were combined, only the association between age and DJD was signifi-cant (Po .0001). For each 1-year increase in cat age, the expected total DJD scoreincreases by an estimated 13.6% (95% confidence interval: 10.6%, 16.8%).Conclusion: Radiographically visible DJD is very common in domesticated cats,even in young animals and is strongly associated with age.Clinical Relevance: DJD is a common disease of domesticated cats that requiresfurther investigation of its associated clinical signs.

Despite recent attempts to characterize feline degenerativejoint disease (DJD) by radiographic changes and associ-ated clinical signs,1,2 surprisingly little is known.

Beadman et al3 reported the first extensive radio-graphic evaluation of DJD of the feline axial skeleton andsubsequent studies1,2,4,5 suggest that the most frequent siteof axial skeletal DJD is T7-10. The most severe lesions ap-pear to be in the lumbar or lumbosacral region. The inci-dence of axial skeleton DJD is markedly different betweenstudies, likely reflecting an increase in frequency of axialskeleton DJD with age. The most commonly affected ap-pendicular joints are the hip and elbow, followed by stifleor possibly tarsus1,2,4–8; however, we are unaware of stud-ies that evaluate every joint in a randomly selected popula-tion of cats to ascertain the prevalence of DJD. Little isknown about the cause of feline DJD, and it is possible it

may be associated with other systemic disease, environ-mental, or management factors.

Our purpose was to evaluate the prevalence of radio-graphic signs of DJD in a sample of cats between 6 monthsand 20 years of age, selected at random from a populationof domestic cats. Further, we evaluated associationsbetween severity of radiographic DJD, and patient demo-graphics, serum biochemical, hematologic, and urinalysisprofile variables.

MATERIALS AND METHODS

This prospective, observational study was approved by ourinstitutional Animal Care and Use Committee. All clientssigned a consent form after being fully informed about the

Veterinary Surgery 39 (2010) 535–544 c� Copyright 2010 by The American College of Veterinary Surgeons 535

mailto:[email protected]

study and the risks associated with participation. Using adatabase of 1640 cats from a single veterinary practice, asample of 100 cats was randomly selected for study as de-scribed below. We wanted to evaluate cats across a broadrange of ages while concurrently selecting cats randomlyfrom this population. To achieve this, cats in the databasewere divided into 4 age groups (6 months to 5 years; 5–10years; 10–15 years; and 15–20 years old). Cats that were ex-actly 5, 10, or 15 years old were assigned to the 6 months–5years, 5–10 years, and 10–15 years groups, respectively.

Within each age group, each cat was assigned a uniquenumber, and then the cats in each group were randomlyranked using shuffled cards. All cats were included, regard-less of health status. The first 25 cats in each age groupwhose owners were willing to participate in the study wereincluded. Owners were contacted in order of ranking, andwere sent up to 2 recruitment letters at 1-month intervals,and then contacted by telephone. If there was no response,or they declined, the next randomly selected owner wascontacted. The investigators worked diligently to persuadeowners to enroll the selected cats.

Once selected, owners visited the NCSU VeterinaryTeaching Hospital and each cat had a general physical ex-amination and body condition score (BCS) performed usinga 5-grade body index system (1-emaciated; 2-thin; obviousabdominal waist; 3-ideal; 4-overweight; no observable ab-dominal waist; 5-obese).9 Age, weight, sex, BCS, amount oftime spent indoors and outdoors, vaccination status (rabies,FeLV, FVRCP), and percentage (%) of the diet that was dryfood were recorded. Hematologic and serum biochemicalprofile analysis, fructosamine and T4 levels, FeLV/FIV test-ing, and urinalysis (specimen collected by cystocentesis) wereperformed after completion of radiographs.

Radiographic Technique

Each cat was sedated for radiographic examination using acombination of ketamine (3–5mg/kg), butorphanol(0.3–0.4mg/kg), and medetomidine (10–15mg/kg) adminis-tered intramuscularly. Doses were adjusted where it wasconsidered clinically appropriate. Medetomidine was re-versed with atipamezole administered intramuscularly (5times the dose [mg] of medetomidine administered) aftercompletion of the radiographic study. Cats with cardiacdisease (auscultable murmurs with or without clinicalsigns) were sedated with a combination of buprenorphine(30mg/kg) and acepromazine (0.03mg/kg) intramuscularly.The lead investigator and technician (A.T.) was present forthe duration of sedation of every cat, and every cat wasmonitored during recovery.

Orthogonal radiographs of all joints and the spine weretaken using an indirect digital flat panel imaging system(CanonMedical CXDI-50G Sensor, Eklin Medical Systems,Santa Clara, CA). Radiographs were centered on the mid-point of the limb or spinal segment. Radiography continueduntil good quality orthogonal projections of every joint oraxial segment were obtained. Quality control was performedby the lead investigator and the radiology technicians.

Radiographic Interpretation

Criteria for evaluation of radiographic signs of felineappendicular joints and axial skeleton DJD were estab-lished by 3 board-certified radiologists (I.R., J.B., A.P.)and 1 board-certified surgeon (B.D.X.L.). Additionalassistance was provided by 1 author (M.F.) who had beeninvestigating the relationship between radiographic fea-tures of feline DJD and the histologic appearance of joints.Criteria were established after detailed evaluation and dis-cussion of radiographs taken in the same manner from aseparate group of 30 cats that were being evaluated as partof a different feline DJD study. Once the criteria for eval-uation of radiographic signs of DJD were defined, theradiographs were assessed by 2 of the board-certifiedradiologists (J.B., A.P.) and a board-certified surgeon(B.D.X.L.). Stored digital radiographs (Amicas PACS,Amicas Inc., Boston, MA) were viewed by each assessorusing e-film (eFilm 3.1, Merge Healthcare, Milwaukee,MI) on 24 in. high-resolution color computer monitors(Dell, Round Rock, TX) calibrated for viewing digitalradiographs.

The manus and pes were considered as 1 joint region forevaluation purposes. Other appendicular joints evaluatedwere carpus, elbow, shoulder, tarsus, stifle and hip. Radio-logic features evaluated and considered indicative of pres-ence of DJD in appendicular joints were: joint effusion (notscored for the hip), osteophytes, enthesophytes, joint-asso-ciated mineralization, sclerosis, subluxation, subchondralbone erosions and cysts, presence of intraarticular mineral-izations (including suspected meniscal mineralizations in thestifle joints) and new bone formation in the intertarsal andtarsometatarsal joints (tarsus only).

To ensure the evaluators carefully evaluated everyfeature, they were required to record a grade for each ofthe features listed above on a worksheet. Then they madeand recorded a subjective overall assessment of DJD sever-ity. A scale (0–4) was used for grading the severity of eachof the radiographic changes identified (0=normal;1= trivial; 2=mild; 3=moderate; 4= severe). Afterthis, a subjective radiographic DJD score (termed ‘‘overallDJD score’’; 0–10) where 0=no radiographic abnormali-ties identified and 10=ankylosis, was assigned to eachjoint based on presence of radiographic changes and theirseverity. This 2nd grading system was the one used forevaluation of prevalence of DJD (see Fig 1 for representa-tive examples).

The axial skeleton was evaluated by dividing thespine into cervical, thoracic and lumbar segments, andlumbosacral region. Radiographic features evaluatedand considered indicative of DJD in the axial skeletonwere: osteophytes, spondylosis, disc-associated degenera-tion (end plate sclerosis, erosion, disc mineralization,narrowing), and subluxation. The same scale (0–4) andan overall subjective radiographic DJD score, as describedfor the appendicular joints, were assigned to each spinalsegment based on presence of radiographic changes andtheir severity.

536 Veterinary Surgery 39 (2010) 535–544 c� Copyright 2010 by The American College of Veterinary Surgeons

Lascelles et alDegenerative Joint Disease in Domestic Cats

Data and Statistical Analysis

Agreement analysis was performed on the overall DJD scoresfor individual appendicular joints and spinal segments. Thiswas done by calculating Fleiss’ kappa (k) statistic10 for eachof the overall DJD scores (0–10) and overall Fleiss’ k statisticsand intraclass correlation (ICC) values for each of the joints.Additionally, the overall DJD scores assigned by each indi-vidual for each appendicular joint or spinal segment were re-defined and grouped on a 1–5 scale as follows: 0 (1, none); 1(2, trivial); 2–4 (3, mild); 5–7 (4, moderate); 8–10 (5, severe).This was done because not all the scores on the 0–10 scale hadbeen used in assigning scores, making agreement analysis forindividual scores impossible. Fleiss’ k statistics for each of thegrouped DJD scores and overall k statistics and ICC valuesfor each of the appendicular joints and spinal segments wereagain calculated. Observer agreement k and ICC values wereinterpreted as suggested by Landis and Koch11: � 0=noagreement; 0.0–0.2= slight agreement; 0.2–0.4= fair agree-ment; 0.4–0.6=moderate agreement; 0.6–0.8=substantialagreement; and 0.8–1.0=almost perfect agreement.

To determine the overall DJD score for each append-icular joint or spinal segment of each cat, the median of thescores assigned by each of the 3 assessors was calculated.

Descriptive statistics were used to describe thenumber of cats with DJD in the appendicular andaxial skeleton (‘‘yes’’ or ‘‘no’’ approach); the summed se-verity for total, appendicular and axial DJD in eachcat (where summed severity equaled the addition ofall the individual overall DJD scores for every partof the skeleton, for all the appendicular joints or all the ax-ial segments, respectively); the most frequently affected ap-pendicular joints and spinal segments, and the medianseverity of DJD in each appendicular joint and spinalsegment. The frequency of bilateral disease was also calcu-lated.

Poisson’s log-linear regressionmodels were initially usedtomodel appendicular, axial, and total DJD scores, each as afunction of a single explanatory variable. The explanatoryvariables considered were sex, bodyweight, BCS, % of timespent indoors/outdoors, vaccination status (rabies, FeLV,FVRCP), use of flea/tick preventatives, FeLV and FIVstatus, hematologic, serum biochemical, and urinalysisprofile variables. The Poisson regression model assumes thatthe response variable Y (in this case, appendicular, axial,or total DJD score) follows a Poisson distribution with log(E (Y|x))= a1bx where a and b are unknown parameters, xis an explanatory variable, and E (Y|x) is the expected value

Figure 1 Representative radiographic images of elbows with various grades (0–10) of degenerative joint disease, illustrating the grading system used

in the present study. Images opposite each other are orthogonal views of the same joint. A and B: grade 0; C and D: grade 1; E and F: grade 3; G–I:

grade 6 (I is an oblique view showing suspected capsular mineralization); J and K: grade 9.


Lascelles et al Degenerative Joint Disease in Domestic Cats

(mean) of Y given x. It follows that

EðYjxþ 1ÞEðYjxÞ ¼ expfaþ bðxþ 1Þg

expfaþ bxg ¼ expfbg

The result of this equation was used to describe howthe explanatory variable x influences the expected value ofY: for each 1 unit increase in x, the expected value of Ychanges by a multiplicative factor of exp {b}.

Sample variances of the DJD scores were greater thanthe sample means, so a quasi-Poisson regression model wasused to account for over dispersion. The model was notadjusted by truncation to account for the natural maxi-mum upper bound for the DJD scores because the esti-mated probability of observing a DJD score greater thanthe upper bound, obtained from fitting the quasi-Poissonregression model, was very small.

RESULTS

Twenty-five cats in each age group were successfully re-cruited and enrolled in the study. Of the owners contacted,19 declined enrollment in the 6 month–5-year age group, 16each in the 5–10 year and the 10–15 year groups, and 45 inthe 15–20 year group. Of the 45 in the 15–20 year group, 16were deceased. Of the 100 cats recruited, 18 were purebredand 82 were domestic short or long hair. Overall mean(� SD) age was 9.42� 5.07 years. Mean bodyweight was5.13� 1.64 kg (range, 2.08–10.16 kg). Median BCS was 3(range, 1–5). Polyarthropathy was not suspected in any caton physical examination. No morbidity or mortality oc-curred with the sedation protocol.

There was significant overall agreement (the null hy-pothesis of k=0 was rejected at the 99% confidence levelfor each body region) between observers when agreementwas assessed using the individual overall DJD scores (1–10)assigned; however this agreement was only fair to moderate(Tables 1 and 2). When DJD scores were grouped intonone, trivial, mild, moderate and severe (as describedabove), agreement between observers was improved, beingfair for the pes, moderate for the carpus, elbow, shoulderand hip joints, and the cervical, thoracic, and lumbosacralspinal segments and substantial for the tarsal and stiflejoints, and the lumbar spinal segment (Tables 3 and 4). Theagreement between observers is summarized for each mainappendicular joint and spinal segment using Tukey’s mean-difference plots (Fig 2).

Ninety-one percent of the cats had at least 1 append-icular joint with DJD (median of 5 joints affected in the 91cats; Fig 3). Figure 4 shows the observed total cat DJDscore versus the cat age. The solid line shows the expected(or predicted) total DJD scores from the quasi-Poisson re-gression model. The most frequently affected joints werehip, followed by stifle, tarsus, and then elbow (Table 5).There was no difference between the number of jointsaffected on the right and left side. Fifty-five percent of thecats had axial skeleton DJD (median of 2 axial segmentsaffected in the 55 cats). The thoracic segment was the most

frequently affected, followed by the lumbosacral region(Table 6).

Overall, 92% of the cats had radiographic evidence ofDJD somewhere in the skeleton. These cats had a mean ageof 9.9 years and mean weight of 5.15 kg. The most severelyaffected joint was the elbow, and the most severely affectedspinal segment was the lumbosacral region (Tables 5 and6). Bilateral disease was common, particularly so for thehip, carpus, elbow, and stifle (Table 7).

There was no evidence of association between DJDscores and the variables sex, % of time spent indoors/out-doors, vaccination status (rabies, FeLV, FVRCP), use offlea/tick preventatives, and FeLV or FIV status. However,many of the explanatory variables considered were foundto be significant predictors of appendicular DJD, axialDJD, and total DJD scores when considered individually(Tables 8–10).

Age was found to be the most important of the ex-planatory variables considered. When a more generalquasi-Poisson regression model was used that includedmultiple explanatory variables simultaneously, no otherexplanatory variables were found to be significant after ac-counting for age. There was overwhelming evidence thatthe total DJD score changes with the age of a cat (P-valueo .0001), and for each 1-year increase in the age of acat, the expected total DJD score increases by an estimated13.6% (95% confidence interval: 10.6–16.8% increase).

DISCUSSION

We found that the prevalence of DJD is high in domesticcats confirming previous retrospective studies1–5,8; how-ever, the population we used for this prospective study mayintroduce some bias. Every attempt was made to randomlyselect subjects, and to that end, a single veterinary practicedatabase was chosen. This was a feline-only veterinarypractice and this may have introduced bias such as life-style, feeding, and veterinary care that may be different inthese cats compared with the broader cat population as a

Table 1 Fleiss k Values and 95% Confidence Intervals (CI) for Agree-

ment Between Observers for Overall DJD Scores (0–10) for Different

Musculoskeletal Regions

Manus Estimate CI Lower CI Upper

Carpus 0.363 0.291 0.434

Elbow 0.335 0.279 0.391

Shoulder 0.443 0.369 0.518

Pes 0.327 0.213 0.440

Tarsus 0.524 0.465 0.584

Stifle 0.558 0.485 0.631

Hip 0.454 0.395 0.513

Cervical 0.358 0.293 0.423

Thoracic 0.534 0.469 0.599

Lumbar 0.448 0.380 0.516

Lumbosacral 0.512 0.452 0.573

All P-values o .001.

DJD, degenerative joint disease.



whole. Cats in our study were from the central North Car-olina region of the United States of America, and geo-graphical differences in the prevalence of DJD may existbetween populations because of environmental or geneticinfluences, just as they do in people.12

We spent considerable time very precisely definingwhat features were to be classified as indicative of DJD incats. There is very little information on the association be-tween radiographic features and gross or histologic fea-tures of DJD in feline joints, and it is possible the featureswe assessed were not indicative of actual joint pathology.We found that several radiographic features not normallyobserved in canine patients (such as medial meniscal min-eralization and periarticular mineralizations were seencommonly in these cats. It could be argued that the inclu-sion of such features as indicative of DJD is erroneous, butwe included such features on the basis of other work wehave performed that has demonstrated an association be-tween those features and DJD as measured by macroscopiccartilage damage. For example, we have observed thatjoints with only meniscal mineralization, and no otherfeatures of DJD, predictably have cartilage erosion.13 In

the present study, joints with only meniscal mineraliza-tion were therefore included in the ‘‘DJD’’ category. Previ-ous studies have included such features as periarticularmineralization as being indicative of DJD.5 Despite longdiscussions spent defining what each assessor was going toscore as DJD, agreement between the observers was onlyfair to moderate, and improved when several broad cate-gories of severity of DJD were used. The more score op-tions there are for the radiologist to choose from the morelikely their scores would not match exactly. For this rea-son, and because it is maybe more appropriate in the clin-ical environment, we combined scores into groups. Itwas clear from conducting this study and a previous pilotstudy, that further work is needed to define the features offeline DJD.

To our knowledge, this is the first prospective study toevaluate every part of the skeletal system for DJD in a ran-domly selected cohort of cats. Similar to previous retro-spective reports of axial skeleton DJD3–5 the mostcommonly affected spinal region was the thoracic segment,followed by the lumbosacral area. However, the thoracicsegment has more vertebrae than other areas, which mayintroduce a bias for it to be affected more often. Othershave suggested the lumbosacral area is the most severelyaffected spinal segment in the cat.4 Review of publishedretrospective studies suggests they support the current find-ing of a strong association between the prevalence of axialDJD and age.3–5 Although it appears that investigators aredescribing the same general findings for axial skeletonDJD, the nomenclature used varies, as do the features in-cluded as being indicative of axial DJD.2–5,14 This problemhas been recently discussed.15 Further studies are needed toaccurately define the features of axial skeleton DJD.

The very high prevalence of appendicular skeletonDJD, and its association with age in our study is supportedby previous reports.4,5,8,16 We found the most commonlyaffected appendicular joints were the hip, followed by stifle,tarsus, and elbow. Previous reports have suggested the el-bow1,4,8,16 and hip2,5 as being most commonly affected.Only 2 of these studies1,2 involving a total of 41 cats

Table 2 ICC Values and 95% Confidence Intervals (CI) for Agreement

Between Observers for Overall DJD Scores (0–10) for the Different

Parts of the Musculoskeletal System Assessed


Carpus 0.789 0.721 0.845

Elbow 0.850 0.799 0.891

Shoulder 0.917 0.887 0.941

Pes 0.330 0.206 0.457

Tarsus 0.896 0.859 0.925

Stifle 0.921 0.892 0.944

Hip 0.873 0.829 0.909

Cervical 0.753 0.677 0.818

Thoracic 0.794 0.728 0.849

Lumbar 0.800 0.735 0.854

Lumbo-sacral 0.868 0.822 0.905


DJD, degenerative joint disease; ICC, intraclass correlation.

Table 3 Fleiss k Values and 95% Confidence Intervals (CI) for Agree-

ment Between Observers for Grouped DJD Scores (1–5, Designating

None, Trivial, Mild, Moderate, and Severe, Respectively)


Carpus 0.401 0.317 0.486

Elbow 0.536 0.463 0.610

Shoulder 0.488 0.409 0.567

Pes 0.327 0.213 0.440

Tarsus 0.602 0.527 0.676

Stifle 0.614 0.538 0.691

Hip 0.565 0.493 0.636

Cervical 0.571 0.495 0.646

Thoracic 0.523 0.442 0.605

Lumbar 0.624 0.552 0.696

Lumbosacral 0.512 0.452 0.573



Table 4 ICC Values and 95% Confidence Intervals (CI) for Agreement

between Observers for Grouped DJD Scores (1–5, Designating None,

Trivial, Mild, Moderate, and Severe, Respectively)


Carpus 0.668 0.575 0.750

Elbow 0.817 0.757 0.867

Shoulder 0.814 0.753 0.864

Pes 0.330 0.206 0.457

Tarsus 0.830 0.773 0.876

Stifle 0.852 0.801 0.893

Hip 0.788 0.720 0.844

Cervical 0.784 0.715 0.841

Thoracic 0.756 0.680 0.819

Lumbar 0.866 0.820 0.903

Lumbosacral 0.868 0.822 0.905


DJD, degenerative joint disease; ICC, intraclass correlation.



evaluated every joint. The other studies evaluated radio-graphs that were available (often thorax or abdomen), andso bias was introduced because only certain joints were vis-

ible on the radiographs. We included meniscal mineraliza-tion as indicative of DJD, and this contributed to the highprevalence of DJD in the stifle joint. This was done because

J

0 1 2 3 4 5

−0.5

1.5

1.0

0.5

0.0

2.0

−0.5

1.5

1.0

0.5

0.0

2.0A B C

D E F

G H I

0 1 2 3 4 5

−0.5

1.5

1.0

0.5

0.0

2.0

0 1 2 3 4 5

−0.5

1.5

1.0

0.5

0.0

2.0

0 1 2 3 4 5

−0.5

1.5

1.0

0.5

0.0

2.0

0 1 2 3 4 5

−0.5

1.5

1.0

0.5

0.0

2.0

0 1 2 3 4 5

−0.5

1.5

1.0

0.5

0.0

2.0

0 1 2 3 4 5

−0.5

1.5

1.0

0.5

0.0

2.0

−0.5

1.5

1.0

0.5

0.0

2.0

−0.5

1.5

1.0

0.5

0.0

2.0

0 1 2 3 4 5 0 1 2 3 4 5 0 1 2 3 4 5

Figure 2 Tukey’s mean difference plots to summarize the interobserver agreement (A = carpus; B = elbow; C = shoulder; D = tarsus; E = stifle;

F = hip; G = cervical spine; H = thoracic spine; I = lumbar spine; J = lumbosacral spine). On the x-axis are the average scores using the 1–5 scale created

by collapsing the 1–10 overall degenerative joint disease (DJD) scores (1, none = overall DJD scores of 0; 2, trivial = overall DJD scores of 1; 3,

mild = overall DJD scores of 2–4); 4, moderate = overall DJD scores of 5–7; 5, severe = overall DJD scores of 8–10), and on the y-axis is the average of

the absolute value of the differences of the scores between observers. The area of the circle is proportional to the number of times that the (x,y) points

occurred for the 100 cats.



of our gross and histologic observations that meniscal min-eralization, despite some suggestions in the literature,17–20

is associated with cartilage degeneration.13

We found a high percentage of joints to be bilaterallyaffected with DJD. In a study of 292 sets of feline radio-graphs (mean cat age not reported but mean age of clinicpopulation, 8.2 years) evaluated for appendicular OA (de-fined as increased subchondral bone density or periarticu-

lar new bone),8 lesions were bilaterally symmetrical in 41(73%) of the 56 affected cats, with the elbow most com-monly affected.

Overall, despite the high prevalence of radiographicDJD, the severity scores were relatively low. This may re-flect the particular population studied or that the radio-graphic severity of DJD in cats may be less than in dogs.This suggestion has been made in previous studies andneeds further investigation.4,5

As individual variables, bodyweight and BCS werefound to be negatively associated with the severity of axialDJD, but no association was found between these variablesand appendicular or total DJD. Anecdotally, it is oftensuggested that obesity causes DJD in cats, which wouldsuggest a positive relationship would be identified. A causalrelationship has not been proven, but the relationship be-tween being overweight and lameness requiring veterinarycare has been evaluated. Studying 1457 cats over a 4.5-year

0 to 5 5 to 10 10 to 15 15 to 200

5

10

15

20

appendicular

Age range (years)

Nu

mb

er o

f ca

ts w

ith

DJD

axial

25

Figure 3 Prevalence of appendicular and of axial radiographic degener-

ative joint disease (DJD) in cats in different age ranges (n = 25 cats in

each age range). Cats that were exactly 5, 10, or 15 years old were as-

signed to the 6 months–5 years, 5–10 years, and 10–15 years groups,

respectively.

Figure 4 Observed total cat degenerative joint disease (DJD) score

(sum of individual appendicular joint and axial skeleton segment overall

DJD scores) versus the age of the cat. The solid line shows the expected

(or predicted) total DJD scores from the quasi-Poisson regression

model.

Table 5 Number of Individual Joints Affected with DJD in 100 Ran-

domly Selected Cats, and Median Overall DJD Score (on a 0–10 Scale)

per Joint

Joint Number (%) of Joints Affected Median (Range) DJD Score

Hip 131 (65%) 2 (1–8)

Stifle 102 (50%) 1 (1–9)

Tarsus 85 (40%) 2 (1–7)

Elbow 69 (35%) 3 (1–9)

Carpus 32 (15%) 2 (1–7)

Shoulder 28 (14%) 2 (1–8)

Pes 1 (0.5%) –

Manus 0 (0%) –

The manus and pes were considered 1 joint.


Table 6 Number of Individual Spinal Segments Affected with DJD in

100 Randomly Selected Cats, and Median Overall DJD Score (on a 0–10

Scale) per Spinal Segment

Spinal Segment Number of Cats Affected Median (Range) DJD Score

Thoracic 43 2 (1–7)

Lumbosacral 29 4 (1–10)

Lumbar 26 2.5 (1–6)

Cervical 20 3 (1–7)


Table 7 Prevalence of Bilateral DJD in Appendicular Joints

Joint

Number of Cats

with DJD of

One or Both

Joints

Number of Cats

with DJD of

Both Left and

Right Joints

% of Cats with DJD

that have DJD of

Both Left and

Right Joints

Manus 0 0 0

Carpus 19 13 68

Elbow 41 28 68

Shoulder 20 8 40

Pes 1 0 0

Hock 55 30 55

Stifle 63 39 62

Hip 73 58 79




period, investigators found that the risk of developinglameness requiring veterinary attention was significantlyincreased for heavy (hazard ratio=2.9) and obese (hazardratio=4.9) cats.21 It was suggested that excess bodyweight

or a generalized lipid metabolic abnormality might lead tocartilage damage and OA; however, the cause of lamenessand specifically if it was associated with DJD was not eval-uated. In 1 retrospective radiographic study of the

Table 8 Summary Results from Fitting Quasi-Poisson Regression Models Using Each Individual Explanatory Variable and its Relationship to the

Presence of Appendicular DJD

Explanatory Variable

P-Value for

Association

with DJD

Level of Evidence

of Significance

Relationship Between

Variable and DJD

(Positive, 1;

Negative, � )

Estimated % of the Expected DJD

Score Increases or Decreases for

Each 1 Unit Increase in the


Age (years) .0000 Overwhelming 1 10.31

Lipase (IU/L) .0000 1 1.75

Urine pH .0010 Very strong � 30.43

Urine specific gravity .0011 � 0.06

Lymphocytes (103/mL) .0012 � 0.02

% Dry food consumed .0014 � 0.70

Creatinine (mg/dL) .0015 1 51.39

Urea nitrogen (mg/dL) .0023 1 2.30

Cholesterol (mg/dL) .0044 1 0.51

Amylase (IU/L) .0072 1 0.07

Sodium (mmol/L) .0180 Strong 1 7.57

Glucose (mg/dL) .0183 � 0.31

Fructosamine (mmol/L) .0198 � 0.38

Magnesium (mg/dL) .0369 1 76.71

Hemolysis index .0506 Suggestive but inconclusive � 0.94

CK (IU/L) .0598 � 0.03

Osmolality—calculated (mOsm/kg) .0671 1 2.42

Chloride (mmol/L) .0810 1 2.14


Table 9 Summary Results from Fitting Quasi-Poisson Regression Models Using Each Individual Explanatory Variable and its Relationship to the

Presence of Spinal DJD


P-Value for Association

with DJD

Level of Evidence

of Significance


Variable and DJD

Estimated % of the Expected

DJD Score Increases or Decreases

for Each 1 Unit Increase in

the Explanatory Variable


Sodium (mmol/L) .0000 1 22.86

Urine pH .0000 � 59.13



Glucose (mg/dL) .0003 � 0.86

Creatinin (mg/dL) .0004 1 109.95

Osmolality—calculated (mOsm/kg) .0011 Very strong 1 7.03

Lipase (IU/L) .0022 1 2.15


BCS .0032 � 32.63

Weight (kg) .0033 � 27.68

Amylase (IU/L) .0046 1 0.11


Bilirubin total (mg/dL) .0088 � 99.99

Fructosamine (mmol/L) .0159 Strong � 0.61

Phosphorus (mg/dL) .0220 1 49.33

Lymphocytes (103/mL) .0315 � 0.03

Monocytes (103/mL) .0465 1 0.11

CK (IU/L) .0502 Suggestive but inconclusive � 0.06

Hemolysis index .0542 � 2.37

Calcium (mg/dL) .0542 1 39.25

Alkaline phosphatase (IU/L) .0551 1 1.54

Na/K ratio .0784 1 6.14

BCS, body condition score.



prevalence of DJD in cats, no significant association be-tween bodyweight and radiographic signs of DJD wasidentified.5 The initial finding of a negative association be-tween bodyweight and axial DJD is likely explained by theeffect of age on bodyweight—with older cats becominglighter. It is known that cats tend to loose weight and BCSas they age.22,23

We did not specifically categorize the DJD as primaryor secondary, but subjectively, there were very few jointswhere any radiographic indications of a cause were seen(e.g. trauma), and in no case was a polyarthropathy sus-pected. The cause of most feline DJD is unknown, and wethought that evaluation of several variables (patient demo-graphics and serum biochemical, hematologic and urineanalysis profile variables) may lead to testable hypothesesfor the cause(s) of feline DJD. Overall, once age was ac-counted for, there were no variables that were significantlyassociated with DJD, and further interpretation of the re-sults of our study should be performed cautiously. How-ever, this simplistic view ignores the possibility that theremay be associations between some variables and DJD. Forexample, chronic kidney disease is known to become moreprevalent in older cats, but it may be that the same patho-logic processes causing chronic kidney disease also causeDJD. Lipase was very strongly associated with DJD, pos-sibly indicating an association between an inflammatoryprocess (that is also associated with age) and DJD, or theassociation may be the result of decreased renal functionleading to decreased excretion of lipase. This is speculationand further studies are required to test specific hypotheses.

The apparent negative association between append-icular DJD and feeding a dry diet is probably because ofthe strong association between age and type of diet fed—the older the cat in our cohort, the more likely they were tobe fed a higher % of their diet as wet food. This likely re-flects the recommendations of the practice this cohort ofcats was recruited from strongly recommending feedingwet food to older cats.

We found a very high prevalence of appendicular andaxial skeleton DJD in domesticated cats. DJD may indeedbe the most common disease of domesticated cats, and thesignificance of these findings in terms of joint pathologyand clinical signs requires investigation.

ACKNOWLEDGMENTS

This study was funded by Novartis Animal Health, through

their competitive grants program. The authors have no financial

or personal relationships that could possibly influence or inap-

propriately bias this work.

REFERENCES

1. Clarke SP, Bennett D: Feline osteoarthritis: a prospectivestudy of 28 cases. J Small Anim Pract 2006;47:439–445

2. Lascelles BD, Hansen BD, Roe S, et al: Evaluation ofclient-specific outcome measures and activity monitoring tomeasure pain relief in cats with osteoarthritis. J Vet InternMed 2007;21:410–416

Table 10 Summary Results from Fitting Quasi-Poisson Regression Models Showing Significant Individual Explanatory Variables and their Relation-

ship to the Presence of Total DJD


P-Value for Association

with DJD

Level of Evidence

of Significance


Variable and DJD

Estimated % of the Expected

DJD Score Increases or Decreases

for Each 1 Unit Increase in

the Explanatory Variable


Lipase (IU/L) .0000 1 1.86

Urine pH .0000 � 37.95



Creatinine (mg/dL) .0001 1 65.27


Sodium (mmol/L) .0005 1 11.31

Lymphocytes (103/mL) .0011 Very strong � 0.02

Glucose (mg/dL) .0011 � 0.45

Amylase (IU/L) .0013 1 0.08

Osmolality—calculated (mOsm/kg) .0065 1 3.62

Fructosamine (mmol/L) .0070 � 0.45

Cholesterol (mg/dL) .0130 Strong 1 0.47


CK (IU/L) .0257 � 0.04

Hemolysis index .0260 � 1.19

Calcium (mg/dL) .0512 Suggestive but inconclusive 1 22.72

Bilirubin total (mg/dL) .0513 � 98.93

Monocytes (103/mL) .0745 1 0.07

BCS .0752 � 12.53

BCS, body condition score; DJD, degenerative joint disease.



3. Beadman R, Smith RN, King AS: Vertebral osteophytes inthe cat. Vet Rec 1964;76:1005–1007

4. Hardie EM, Roe SC, Martin FR: Radiographic evidence ofdegenerative joint disease in geriatric cats: 100 cases(1994–1997). J Am Vet Med Assoc 2002;220:628–632

5. Clarke SP, Mellor D, Clements DN, et al: Prevalence ofradiographic signs of degenerative joint disease in a hospitalpopulation of cats. Vet Rec 2005;157:793–799

6. Langenbach A, Green P, Giger U, et al: Relationship betweendegenerative joint disease and hip joint laxity by use ofdistraction index and Norberg angle measurement in a groupof cats. J Am Vet Med Assoc 1998;213:1439–1443

7. Keller GG, Reed AL, Lattimer JC, et al: Hip dysplasia: afeline population study. Vet Radiol Ultrasound 1999;40:460–464

8. Godfrey DR: Osteoarthritis in cats: a retrospectiveradiological study. J Small Anim Pract 2005;46:425–429

9. German A,Martin L: Feline Obesity, in Encyclopedia of FelineClinical Nutrition. Aimargues, Royal Canin, 2008, pp 16

10. Fleiss JL: Statistical Methods for Rates and Proportions (ed 2).New York, John Wiley, 1981

11. Landis JR, Koch GG: The measurement of observeragreement for categorical data. Biometrics 1977;33:159–174

12. Ali-Gombe A, Croft PR, Silman AJ: Osteoarthritis of the hipand acetabular dysplasia in Nigerian men. J Rheumatol1996;23:512–515

13. Freire M, Brown J, Robertson I, et al: Meniscalmineralization in domestic cats. Vet Surg 2010, doi: 10.1111/j.1532-950X.2010.00648.x.

14. Rothschild BM, Rothschild C, Woods RJ: Inflammatoryarthritis in large cats: an expanded spectrum ofspondyloarthropathy. J Zoo Wildl Med 1998;29:279–284

15. Lascelles BD: Feline degenerative joint disease. Vet Surg2010;39:2–13

16. Pacchiana PD, Gilley RS, Wallace LJ, et al: Absolute andrelative cell counts for synovial fluid from clinically normalshoulder and stifle joints in cats. J Am Vet Med Assoc 2004;225:1866–1870

17. Ganey TM, Ogden JA, Abou-Madi N, et al: Meniscalossification. II. The normal pattern in the tiger knee. SkeletalRadiol 1994;23:173–179

18. Reinke J, Mughannam A: Meniscal calcification andossification in six cats and two dogs. J Am Anim Hosp Assoc1994;30:145–152

19. Walker M, Phalan D, Jensen J, et al: Meniscal ossiclesin large non-domestic cats. Vet Radiol Ultrasound 2002;43:249–254

20. Whiting PG, Pool RR: Intrameniscal calcification andossification in the stifle joints of three domestic cats. J AmAnim Hosp Assoc 1984;21:579–584

21. Scarlett JM, Donoghue S: Associations between bodycondition and disease in cats. J Am Vet Med Assoc1998;212:1725–1731

22. Kronfeld DS, Donoghue S, Glickman LT: Body condition ofcats. J Nutr 1994;124:2683S–2684S

23. Laflamme DP: Nutrition for aging cats and dogs and theimportance of body condition.Vet Clin North Am Small AnimPract 2005;35:713–742



57

pUBLICATION 2

Radiographic evaluation of feline appendicular degenerative joint disease

versus macroscopic appearance of articular cartilage. Freire M, Robertson

I, Bondell HD, Brown J, Hash J, Pease AP, Lascelles BD. Veterinary

Radiology & Ultrasound. 2011;52(3):239-47.











RADIOGRAPHIC EVALUATION OF FELINE APPENDICULAR

DEGENERATIVE JOINT DISEASE VS. MACROSCOPIC APPEARANCE

OF ARTICULAR CARTILAGE

MILA FREIRE, IAN ROBERTSON, HOWARD D. BONDELL, JAMES BROWN, JON HASH, ANTHONY P. PEASE,B. DUNCAN X. LASCELLES

Degenerative joint disease (DJD) is common in domesticated cats. Our purpose was to describe how radio-

graphic findings thought to indicate feline DJD relate to macroscopic cartilage degeneration in appendicular

joints. Thirty adult cats euthanized for reasons unrelated to this study were evaluated. Orthogonal digital

radiographs of the elbow, tarsus, stifle, and coxofemoral joints were evaluated for the presence of DJD. The

same joints were dissected for visual inspection of changes indicative of DJD and macroscopic cartilage damage

was graded using a Total Cartilage Damage Score. When considering all joints, there was statistically sig-

nificant fair correlation between cartilage damage and the presence of osteophytes and joint-associated min-

eralizations, and the subjective radiographic DJD score. Most correlations were statistically significant when

looking at the different joints individually, but only the correlation between the presence of osteophytes and the

subjective radiographic DJD score with the presence of cartilage damage in the elbow and coxofemoral joints

had a value above 0.4 (moderate correlation). The joints most likely to have cartilage damage without ra-

diographic evidence of DJD are the stifle (71% of radiographically normal joints) followed by the coxofemoral

joint (57%), elbow (57%), and tarsal joint (46%). Our data support radiographic findings not relating well to

cartilage degeneration, and that other modalities should be evaluated to aid in making a diagnosis of feline

DJD. r 2011 Veterinary Radiology & Ultrasound, Vol. 52, No. 3, 2011, pp 239–247.

Key words: cartilage damage, cat, DJD, macroscopic, radiographs.

Introduction

FELINE DEGENERATIVE JOINT disease (DJD) is common in

domesticated cats.1–5 The high prevalence has gener-

ated interest in describing the clinical signs, evaluating

causes and predisposing factors, and measuring the pain

associated with the radiographic changes.6–12 Despite this

interest, there is no information on how the radiographic

findings of feline DJD relate to actual degeneration of the

various joint components, such as cartilage.

Grading of DJD in animals and human patients is usu-

ally performed using radiographic imaging and evaluation

of cartilage changes during surgery or arthroscopy. How-

ever, the usefulness of various radiographic features of

DJD for prediction of articular cartilage degeneration is

not well documented in any species. In humans, marginal

osteophytes may be the most sensitive radiographic feature

for the detection of articular cartilage degeneration in the

patellofemoral joint.13,14

Historically, radiographic criteria used to assess canine

DJD have been applied to cats 2–4 and it has been assumed

that these criteria are indicative of joint tissue degenera-

tion. However, some have suggested that the radiographic

features of DJD in the cat are different to those in the dog.5

Others have suggested that cats do not form osteophytes as

readily as dogs2,3,5,10; while still others have suggested ra-

diographically normal joints can be a source of pain due to

DJD.3,8 Clearly, there is a need to understand how the

radiographic features of feline DJD relate to joint tissue

degeneration.

High-resolution analog radiographs have increased spa-

tial resolution compared with digital radiographs. Al-

though digital radiographs have poorer spatial resolution,

considered important in feline orthopedic imaging, the as-

sociated enhanced dynamic range and postprocessing ca-

pabilities can lead to an overall improvement in diagnostic

performance.15 There are no studies comparing analog vs.

digital imaging systems with respect to feline extremities.

Funding was provided by Novartis Animal Health, through their globalFellowship Research program.This study was completed at the North Carolina State University Col-

lege of Veterinary Medicine, Raleigh, NC.Address correspondence and reprint requests to B. Duncan X. Lascelles

at the above address. E-mail: [email protected] June 27, 2010; accepted for publication January 18, 2011.doi: 10.1111/j.1740-8261.2011.01803.x

From the College of Veterinary Medicine, 4700 Hillsborough St., Ra-leigh, NC 27606 (Freire, Robertson, Brown, Hash, Pease, Lascelles); De-partment of Statistics, North Carolina State University, Box 8203,Raleigh, NC 27695 (Bondell).

239


We hypothesize (null hypotheses) there is no difference

between the sensitivity of digital and analog radiographs

for the detection of radiographic signs of DJD in feline

joints and secondly, that there is no association between

radiographic features of DJD and the presence of macro-

scopically detectable articular cartilage damage in feline

appendicular joints.

Materials and Methods

Thirty adult cats euthanized at a local animal shelter

with an overdose of barbiturates for population control

were studied. We aimed to identify 15 cats with multiple

joint DJD and 15 without radiographically detectable

DJD. We also aimed to have both radiographically normal

joints and joints with varying degrees of radiographic DJD.

The breeds were domestic short hair (23), domestic long

hair (2), domestic medium hair (2), Main Coon (1), Ab-

yssinian (1), and Himalayan (1). They were nine neutered

male, two intact male, six neutered female, and 13 female

cats; cats were considered neutered female when neuter

status was not known. The mean (� SD) age of the cats

was 12 years (� 4); age was known in 25 cats. Mean weight

was 4.75kg (� 0.957) and the median body condition score

was 3/5. A total of 60 elbow, 60 tarsal, 60 stifle, and 59

coxofemoral joints were included in the study. One coxo-

femoral joint was excluded because of the presence of an

intraarticular fracture of the femoral head.

Within 1h of euthanasia, orthogonal radiographs of the

elbow (medio-lateral and caudo-cranial views), tarsus

(medio-lateral and dorso-plantar views), stifle (medio-lat-

eral and cranio-caudal views), and coxofemoral joints (lat-

eral and extended ventro-dorsal views) were made using an

indirect digital flat panel imaging system� and high detail

film/screen (analog) system.w,zThe digital and analog radiographs were evaluated by a

group of three board-certified veterinary radiologists (I.R.,

J.B., A.P.) and one board-certified veterinary surgeon

(B.D.X.L.). Assessments were the consensus of all individ-

uals. Digital radiographs were viewed using Dell Ultra-

sharp 2407WFP color monitors (2400 LCD resolution of

1920� 1200) and standard medical image viewing soft-

ware.y Evaluations were performed without knowledge of

the age, breed, gender, or macroscopic appearance of the

joints. Using radiographs from 10 randomly selected cats,

the assessors discussed what radiographic features to score

that were indicative of DJD. Radiographic features de-

cided upon were increased soft tissue opacity within the

joint considered compatible with joint effusion, osteo-

phytes, enthesophytes, joint-associated mineralization—

extraarticular mineralizations considered to be outside

the joint, possibly associated with joint capsule or ten-

dons, sclerosis, subchondral bone erosions/cysts, coxofem-

oral subluxation, intraarticular mineralizations—including

meniscal mineralizations, and new bone formation on the

dorsal surface of intertarsal and tarsometatarsal joints.

A severity scale from 0 to 4, constructed by the assessors,

was used for grading the severity of each radiographic

change (0 normal, 1 trivial, 2 mild, 3 moderate, 4 severe)

for each joint. Following this a subjective radiographic

DJD score (DJD/10) from 0 to 10 (0—no radiographic

abnormalities identified; 10—ankylosis) was assigned to

each joint based on the presence of radiographic changes

and their severity.

Following radiographic evaluation, each joint was

opened carefully by one of the authors (M.F.), who did

not participate in radiographic interpretation, for visual

inspection and evaluation of degenerative changes. Mac-

roscopic changes considered indicative of DJD were

osteophytes, joint-associated mineralization, and cartilage

damage.

Osteophytes were graded according to the osteophyte

scoring system described in a previous study16: Grade 0—

normal; Grade 1—small osteophytes; Grade 2—medium

osteophytes; Grade 3—large osteophytes. Joint-associated

mineralizations were graded based on size using the fol-

lowing scale: Grade 0—none; Grade 1—mild mineraliza-

tion; Grade 2—moderate mineralization; Grade 3—large/

extensive mineralization. The surface appearance of the

joints was evaluated grossly for fibrillation and/or erosion

of the articular cartilage using application of India ink as

described previously.17 The cartilage surface was painted

with India ink twice, rinsing the cartilage with water each

time, 3min after the ink was applied. The severity of sur-

face cartilage damage was scored based on ink retention,

and graded according to the scale described in a previous

study18:Grade 1—Intact surface: surface appears normal

and does not retain any ink; Grade 2—Minimal fibrilla-

tion: site appears normal before staining, but retains India

ink as elongated specks or light grey patches; Grade 3—

Overt fibrillation: the cartilage is velvety in appearance and

retains ink as intense black patches. Grade 4—Erosion:

loss of cartilage exposing the underlying bone.

The severity of articular cartilage damage for each joint

was quantified as the Total Cartilage Damage Score, which

was the sum of the Cartilage Damage Score of each main

articular surface of that joint. The Cartilage Damage Score

of each of those areas was calculated as the percent of the

total articular cartilage area damaged, multiplied by the

degree of cartilage damage for that area based on the ink

retention grading system. The Cartilage Damage Score

ranged from 0 to 400 (0—no cartilage damage; 400—com-

plete exposure of subchondral bone over the whole of the

�Canon Medical CXDI-50G Sensor, Eklin Medical Systems, SantaClara, CA.wKodak Lanex Fine screens, Carestream Health, Rochester, NY.zSuper HR-U 30 X-ray film, Fuji Medical Systems, Stamford, CT.yeFilm 2.1.2Merge Healthcare, Milwaukee, WI.

240 FREIRE ET AL 2011

articular surface) and was calculated using the following

equation:

CartilageDamageScore

¼ ½%area1 � ink gradearea 1�þ ½%area2 � ink gradearea 2� þ � � �

The Total Cartilage Damage Score was the addition of

the Cartilage Damage Score for each main articular sur-

face(s) of each bone comprising the joint:

TotalCartilageDamage Scoreelbow

¼ CartilageDamage Scoreulna

þ CartilageDamage Scoreradius

þ CartilageDamage Scorehumerus

TotalCartilageDamage Score coxofemoral

¼ CartilageDamage Scoreacetabulum

þ CartilageDamage Scorefemoral head

Total CartilageDamage Scoretarsus

¼ CartilageDamageScoretalus

þ CartilageDamage Scoretibia

TotalCartilageDamageScore stifle

¼ CartilageDamage Scorefemurmed condyle

þ CartilageDamageScorefemur lat condyle

þ CartilageDamageScorefemur trochlea

þ CartilageDamageScoretibiamed condyle

þ CartilageDamageScoretibia lat condyle

þ CartilageDamageScorepatella

Total Cartilage Damage Score values ranged from 0 to

1200 in the elbow, 2400 in the stifle, 800 in the tarsus, and

800 in the coxofemoral joint (0—no cartilage damage

present; highest value—complete exposure of subchondral

bone in all articular surfaces evaluated).

To calculate the Cartilage Damage Score and Total

Cartilage Damage Score, digital photographs of the major

joint surfaces, after the second application and washing off

of India ink, were made in exactly the same way in each

joint. Computer softwarez was used to calculate the per-

cent of the cartilage area retaining India ink as a result of

cartilage fibrillation.

To assess the correlation between the analog and digital

radiographic scores Kendall’s t correlation coefficient was

used. The radiographic scores considered were: subjective

overall radiographic DJD score for the joint (0–10), Yes/

No DJD (whether or not DJD was present; score 1–0) and

the main radiographic features considered indicative of

DJD (scored on the 0–4 scale).

After the digital and analog radiographic scores were

correlated, Wilcoxon’s signed-rank test was used to com-

pare the sensitivity of the two systems. As a result of these

comparisons, digital radiographic data were used in the

remainder of the study.

The prevalence of radiographic signs of DJD in digital

radiographs and macroscopic evidence of cartilage damage

was characterized using descriptive statistics. The correla-

tion between the India ink score for each joint and the

subjective radiographic DJD score (DJD/10) as well as the

severity scores for the main radiographic features of DJD

was computed using Kendall’s t correlation coefficient.

Kendall’s t coefficient results were interpreted as follows: 0,

negative correlation; 0–0.2, slight correlation; 0.21–0.4, fair

correlation; 0.41–0.6, moderate correlation; 0.61–0.8, sub-

stantial correlation; 0.81–1, almost perfect correlation.

The mean (� SD) Total Cartilage Damage Score for

those joints with an overall subjective radiographic DJD

score of 0 was calculated to quantify the degree of cartilage

damage present when there were no radiographic signs of

DJD. Finally, multiple linear regression was used in each

joint to investigate for relationships between the magnitude

of Total Cartilage Damage Score and age, weight, gender,

BCS, and each of the radiographic findings considered in-

dicative of DJD. The models used were expressed by

TotalCartilageDamage Scoreelbow

¼ b0 þ b1 �DJD=10

þ b2 � osteophytes

þ b3 � joint-associatedmineralizations

þ b4 � sclerosis

þ b5 � effusion

þ b6 � enthesophytes

þ b7 � erosions=cysts

þ b8 � age

þ error

TotalCartilageDamageScoretarsus

¼ b0 þ b1 � DJD=10



þ b4 � sclerosis

þ b5 � effusion


þ b7 � fusion mineralization


þ b9 � age

þ errorzAdobe Photoshop 7.0, Adobe, CA.

241RADIOGRAPHIC DJD VS CARTILAGE APPEARANCE CATSVol. 52, No. 3

TotalCartilageDamageScorestifle

¼ b0 þ b1 � DJD=10



þ b4 � sclerosis

þ b5 � effusion


þ b7 � intraarticularmineralizations

þ b8 � meniscalmineralization


þ b10 � age

þ error

TotalCartilageDamageScorecoxofemoral

¼ b0 þ b1 � DJD=10



þ b4 � sclerosis

þ b5 � subluxation


þ b7 � age

þ error

Total CartilageDamage Score ¼ Dependent variable

b0 ; b1 ; . . . bn ¼ contributionof each independent variable

to the prediction of the dependent variable:In all analyses, Po0.05 was considered significant.

RESULTS

Significant correlation was found between digital and

analog radiographic scores for all features except joint-as-

sociated mineralizations in the stifle and enthesophytes in

the tarsal joint (Table 1). Either there were no differences

between analog vs. digital radiographic scores or digital

radiographic scores were higher than analog radiographic

scores (Table 2). Hence, digital radiographs were consid-

ered more sensitive in the detection of the radiographic

features studied.

Of the 239 joints evaluated for radiographic changes in-

dicative of DJD, changes were found in 127 joints (53%).

Evaluation of Digital Radiographs

Elbow Joint

Twenty-five (42%) of the 60 elbows had radiographic

signs of DJD with a median subjective radiographic DJD

score of 3 (range, 1–5). Joint-associated mineralizations

were identified in 18 elbow joints (72% of joints with ra-

diographic signs of DJD), osteophytes in 16 joints (64%),

enthesophytes in four joints (16%), and sclerosis of the Table1.CorrelationbetweenDigitalandAnalogRadiograp

hsAssessingSubjectiveRadiograp

hicDJD

/10score,Yes/N

oDJD

Score

andMain

Rad

iographicFeaturesConsidered

Indicative

ofDJD

inEach

Joint,Exp

ressed

byKendall’stCorrelationCoefficient

Digital

vsAnalogRadiograp

hs

DJD

/10

DJD

Yes/N

oOsteophytes

JAM

Sclerosis

Effusion

Enthesophytes

Erosions–Cysts

IAM

Tarsal

Fusion

Subluxation

Meniscal

Mineralization

Elbow

Kendall’st

0.81

0.83

0.7

0.64

��

��

Po

0.0001

o0.0001

o0.0001

o0.0001

——

——

Tarsus

Kendall’st

0.63

0.57

0.54

0.59

�1

0.14

�0.54

Po

0.0001

o0.0001

o0.0001

o0.0001

—o

0.0001

0.11

—o

0.0001

Stifle

Kendall’st

0.88

0.89

0.65

—�

�1

�0.89

0.84

Po

0.0001

o0.0001

o0.0001

0.6

——

o0.0001

—o

0.0001

o0.0001

Coxofemoral

Kendall’st

0.42

0.26

0.57

��

��

�0.26

Po

0.0001

0.003

o0.0001

——

——

—0.003

� Insufficientnumber

ofaffectedjointsto

conduct

ameaningfulstatisticalan

alysis.P-values

o0.05

indicatethat

correlationbetweendigital

andanalogfilm

radiographsissignificant.Kendall’st

correlationcoefficientresultswereinterpretedasfollows:0,noornegativecorrelation;0–0.2,

slightcorrelation;0.21–0.4,faircorrelation;0.41–0.6,moderate

correlation;0.61–0.8,substantial

correlation;0.81–1,

almost

perfect

correlation;1,perfect

correlation.JA

M,joint-associatedmineralizations;IA

M,intraarticularmineralizations.


subchondral bone in two joints (8%). Joint effusion or

subchondral erosions–cysts were not seen in any elbow.

Tarsal Joint

Thirty-four (57%) tarsal joints had radiographic DJD

with a median subjective radiographic DJD score of 1

(range, 1–5). New bone formation on the dorsal surface of

intertarsal and tarsometatarsal joints was detected in 26

joints (77% of joints with radiographic signs of DJD); en-

thesophytes in nine joints (27%); joint effusion and joint-

associated mineralizations were identified in six joints each

(18%); osteophytes in five joints (15%); subchondral bone

sclerosis in two joints (6%); subchondral bone erosions–

cysts in one joint (2.9%).

Stifle Joint

Thirty-nine (65%) of the 60 stifle joints had radiographic

DJD with a median subjective radiographic DJD score of 1

(range, 1–5). Intraarticular mineralization was detected in

34 joints (87% of joints with radiographic signs of DJD),

32 of these were classified as meniscal mineralization; joint

effusion in four joints (10%); osteophytes in three joints

(8%); enthesophytes and joint-associated mineralizations

in two joints each (5%); subchondral sclerosis and ero-

sions–cysts were not detected in any stifle joint.

Coxofemoral Joint

Twenty-nine (49%) of the 59 coxofemoral joints had

radiographic DJD with a median subjective radiographic

DJD score of 2 (range, 1–8). Osteophytes were detected in

25 (86% of joints with radiographic signs of DJD), coxo-

femoral subluxation in 12 joints (41%), subchondral scle-

rosis and joint-associated mineralization in three joints

each (10%). Joint-associated mineralization, joint effusion,

enthesophytes, and subchondral erosions–cysts were not

detected in any coxofemoral joint.

Based on India ink staining, macroscopic cartilage dam-

age/fibrillation was present in 166 joints (69% of all the

joints evaluated) with a median value of 2 (range, 1–4).

Complete articular cartilage erosion with exposure of sub-

chondral bone (Cartilage Damage Score 4) was present in

16 joints (7%).

Macroscopic Evaluation of Cartilage

Elbow Joint

Cartilage damage was present in 43 (72%) elbow joints.

The elbow joints with cartilage damage had a median

India ink score of 2 (range, 2–4) and a mean Total Car-

tilage Damage Score of 176 (� 149). Cartilage damage was

seen most often on the ulna, in the area of the medial

coronoid process, and on the corresponding medial

humeral condyle. Of joints with cartilage damage, the

mean Cartilage Damage Scorehumerus was 64 (� 59),

the mean Cartilage Damage Scoreulna was 71 (� 62), and

the mean Cartilage Damage Scoreradius was 41 (� 42).

Tarsal Joint

Cartilage damage was present in 32 (53%) tarsal joints.

The tarsal joints with cartilage damage had a median India

ink score of 2 (range, 2–4) and a mean Total Cartilage

Damage Score of 101 (� 133). Cartilage damage was seen

on the trochlea of the talus and on the corresponding distal

articular surface of the tibia. Of joints with cartilage dam-

age, the mean Cartilage Damage Scoretibia was 52 (� 70)

and the mean Cartilage Damage Scoretalus was 49 (� 66).

Stifle Joint

Cartilage damage was present in 48 (80%) stifle joints.

The stifle joints with cartilage damage had a median India

ink score of 3 (range, 2–4) and a mean Total Cartilage

Damage Score of 115 (� 97). Cartilage damage was

located mainly on the patella and in the medial compart-

ment of the joint, including the medial femoral condyle

Table 2. P-values from the Wilcoxon’s Signed-Rank Test for Comparison of Sensitivity between Digital and Analog Radiographs for Detectionof Radiographic Features Indicative of DJD

Sensitivity of Digital vs Analog Radiographs

DJD/10DJD

Yes/No Osteophytes JAM Sclerosis Effusion EnthesophytesErosions–Cysts IAM

TarsalFusion Subluxation

MeniscalMineralization

Elbow 0.0098 0.37 0.0098 0.13 � � � �

Tarsus o 0.001 0.01 0.1 0.12 � � 0.3 � o 0.001Stifle 0.02 � 0.37 1 � 0.12 � � 0.82 0.65Coxofemoral 0.001 0.13 0.01 � � � � � 0.58

�Insufficient number of affected joints to conduct a meaningful statistical analysis. Significant P-values indicate that the digital radiographs were more

sensitive; nonsignificant P-values indicate there was no difference in sensitivity between digital and analog films. JAM, joint-associated mineral-

izations; IAM, intraarticular mineralizations.


and medial tibial condyle. The lateral femoral and tibial

condyles were less affected. The mean Cartilage Damage

Scorefemur med condyle was 36 (� 44), the mean Cartilage

Damage Scorefemur lat condyle was 5 (� 8), the mean Car-

tilage Damage Scorefemur trochlea was 14 (� 20), the mean

Cartilage Damage Scoretibia med condyle was 17 (� 26), the

mean Cartilage Damage Scoretibia lat condyle was 3 (� 7),

and the mean Cartilage Damage Scorepatella was 41 (� 41).

Coxofemoral Joint

Cartilage damage was present in 43 (73%) coxofemoral

joints. The coxofemoral joints with detectable cartilage

damage had a median India ink score of 2 (range, 2–4)

and a mean Total Cartilage Damage Score of 101 (� 75).

Most cartilage damage was located on the craniodorsal

surface of the femoral head and on the corresponding sur-

face on the acetabulum. The mean Cartilage Damage

Scorefemoral head was 52 (� 40) and the mean Cartilage

Damage Scoreacetabulum was 50 (� 42).

Considering the surfaces measured, and based on the

mean percent cartilage damage, the joint with the greatest

extent of cartilage damage was the elbow joint with a mean

of 10.5% Total Cartilage Damage. The stifle joint was next

most affected with a mean 7.6%, followed by the coxo-

femoral joint with a mean of 6%, and the tarsus with a

mean of 4.4%.

Comparison of Macroscopic Cartilage Damage and

Digital Radiographic Features

When considering all the joints, there was a significant

correlation between the India ink retention score and the

subjective radiographic DJD score as well as the radio-

graphic evidence of osteophytes and joint-associated

mineralizations (Table 3). The other radiographic signs of

DJD that were common to all joints (enthesophytes, joint

effusion, erosions–cysts, and sclerosis) were not present in

enough joints to conduct a meaningful statistical analysis.

In the elbow joint, significant correlation was found

between the India ink retention score and the subjective

radiographic DJD score, osteophytes and the presence of

joint-associated mineralizations (Table 3). Correlation was

not significant between India ink retention score and

the radiographic evidence of sclerosis (P¼ 0.7) or en-

thesophytes (P¼ 0.14). Radiographic features indicative of

joint effusion and subchondral bone erosions/cysts were

not present in enough joints to perform meaningful statis-

tical analysis. The most significant correlation was between

India ink retention score and osteophytes present on digital

radiographs (Kendall’s t¼ 0.52, moderate correlation;

Po0.0001). Twenty (57%) of the 35 elbow joints with no

radiographically detectable DJD had macroscopic cartilage

damage with a median India ink score of 2 (range, 2–3).

Twenty-three (92%) of the 25 elbow joints with radio-

graphically detectable DJD had macroscopic cartilage

damage with a median India ink score of 3 (range, 2–4).

In the tarsal joint, significant correlation was found

between the India ink retention score and the subjective

radiographic DJD score and the radiographic evidence of

osteophytes, joint-associated mineralizations (Table 3),

sclerosis (Kendall’s t¼ 0.33; P¼ 0.0002), joint effusion

(Kendall’s t¼ 0.27; P¼ 0.002), and enthesophytes (Ken-

dall’s t¼ 0.18; P¼ 0.04). The presence of new bone

formation in the dorsal surface of intertarsal and tarso-

metatarsal joints was not correlated significantly with the

India ink retention score (P¼ 0.24). Radiographic evidence

of subchondral bone erosions–cysts was not present in

enough joints to conduct meaningful statistical analysis.

The most significant correlation was between India ink re-

tention score and osteophytes present on digital radio-

graphs (Kendall’s t¼ 0.35, fair correlation; P¼ 0.0001).

Twelve (46%) of the 26 tarsal joints with no radio-

graphically detectable DJD had macroscopic cartilage

damage with an ink score of 2. Twenty (59%) of the 34

tarsal joints with radiographically detectable DJD had

macroscopic cartilage damage with a median India ink

score of 2 (range, 2–4).

In the stifle joint, significant correlation was found be-

tween the India ink retention score and the subjective

radiographic DJD score (Kendall’s t¼ 0.28; P¼ 0.001),

intraarticular mineralizations (Kendall’s t¼ 0.32; P¼0.0003), and meniscal mineralization (Kendall’s t¼ 0.25;

P¼ 0.004). No significant correlation was found between

the India ink retention score and the radiographic

evidence of osteophytes (P¼ 0.055), joint-associated

mineralizations (P¼ 0.12), joint effusion (P¼ 0.3), or

enthesophytes (P¼ 0.12). Sclerosis and subchondral bone

erosions/cysts were not present in enough joints to conduct

a meaningful statistical analysis. The most significant

correlation was between India ink retention score and

Table 3. Correlation Between Radiographic DJD Scores and India InkScores Using Kendall’s t Correlation Coefficient

Digital Radiographic DJD Scores vs India Ink Scores

DJD/10 Osteophytes JAM

Elbow 0.5 (Po0.0001) 0.52 (Po0.0001) 0.38 (Po0.0001)Tarsus 0.26 (P¼ 0.003) 0.35 (P¼ 0.0001) 0.18 (P¼ 0.043)Stifle 0.28 (P¼ 0.001) 0.17 (P¼ 0.055) 0.14 (P¼ 0.12)Coxofemoral 0.42 (Po0.0001) 0.43 (Po0.0001) 0.23 (P¼ 0.009)All 0.35 (Po0.0001) 0.3 (Po0.0001) 0.26 (Po0.0001)

P-values o0.05 indicate that correlation between digital radiographic

DJD scores and India ink retention scores is significant. Kendall’s tcoefficient results were interpreted as follows: 0, no or negative corre-

lation; 0–0.2, slight correlation; 0.21–0.4, fair correlation; 0.41–0.6,

moderate correlation; 0.61–0.8, substantial correlation; 0.81–1, almost

perfect correlation; 1, perfect correlation. DJD, degenerative joint dis-

ease; JAM, joint-associated mineralizations.


intraarticular mineralization present on digital radiographs

(Kendall’s t¼ 0.32, fair correlation; P¼ 0.0003). Fifteen

(71%) of the 21 stifle joints with no radiographically de-

tectable DJD had macroscopic cartilage damage with a

median India ink score of 2 (range, 2–3). Thirty-three

(85%) of the 39 stifle joints with radiographically detectable

DJD had macroscopic cartilage damage with a median India

ink score of 3 (range, 2–4).

In the coxofemoral joint, significant correlation was

found between the India ink retention score and the sub-

jective radiographic DJD score, the radiographic evidence

of osteophytes, joint-associated mineralizations (Table 3),

and joint subluxation (Kendall’s t¼ 0.21; P¼ 0.017). No

significant correlation was found between the India ink

retention score and the radiographic evidence of sclerosis

(P¼ 0.2). The presence of joint effusion, enthesophytes,

and subchondral bone erosions/cysts were not present in

enough joints to conduct meaningful statistical analysis.

The most significant correlation was between India ink re-

tention score and osteophytes present on digital radio-

graphs (Kendall’s t¼ 0.43, moderate correlation; Po0.0001). Seventeen (57%) of the 30 coxofemoral joints

with no radiographically detectable DJD had macroscopic

cartilage damage with an India ink score of 2. Twenty-six

(90%) of the 29 coxofemoral joints with radiographically

detectable DJD had macroscopic cartilage damage with a

median India ink score of 2 (range, 2–4).

A positive value for mean (� SD) Total Cartilage Dam-

age Score for those joints with subjective radiographic DJD

scored as 0 indicated that cartilage damage was present

without radiographic evidence of DJD. For joints with

subjective DJD scored as 0, the elbow had a mean Total

Cartilage Damage Score of 56 (� 75) (N¼ 35; Po0.0001),

the tarsus had a mean Total Cartilage Damage Score of 27

(� 57) (N¼ 26; P¼ 0.008), the stifle had a mean Total

Cartilage Damage Score of 45 (� 61) (N¼ 21; P¼ 0.0004),

and the coxofemoral joint had a mean Total Cartilage

Damage Score of 49 (� 59) (N¼ 30; Po0.0001).

Based on multiple linear regression analysis, the Total

Cartilage Damage Score was best predicted by osteophyto-

sis and age for the elbow (r2¼ 0.51); sclerosis and age for

the tarsus (r2¼ 0.82); osteophytosis, subjective radio-

graphic DJD score, intraarticular mineralizations and age

for the stifle (r2¼ 0.72); and subluxation and age for the

coxofemoral joint (r2¼ 0.62).

As there were many joints with Total Cartilage Damage

Scores of zero, multiple linear regression was repeated us-

ing a two-step regression model. First a logistic regression

was performed to determine the probability of scores being

nonzero; then given that the scores were nonzero a linear

regression was used. The two-step regression model pro-

duced a best-fit model very similar to the previously de-

scribed model; it included the same factors in the

coxofemoral joint, did not include age in the elbow joint

and the tarsal joint, and it included meniscal mineralization

as a new variable in the stifle joint.

DISCUSSION

We defined a list of radiographic features considered

indicative of feline DJD, based on the radiographic

changes that are identified in joint degeneration of other

species. This was necessary because the radiographic fea-

tures of feline DJD were undefined. It could be argued that

some of the radiographic features scored in this study have

not been proven to be secondary to joint degeneration or

part of the degenerative process, such as dorsal new bone

on the intertarsal and tarsometatarsal joints, joint-associ-

ated mineralizations or meniscal mineralization. For ex-

ample, it has been suggested that periarticular soft tissue

mineralization may not represent DJD.1 However, men-

iscal mineralization is strongly associated with medial

compartment stifle DJD.19 Our data suggests that other

poorly defined radiographic features, such as joint-associ-

ated mineralizations, may also be associated with joint

degeneration.

Digital radiographs were equally or more sensitive for

detection of degenerative changes vs. analog radiographs.

This study was not designed to describe the sensitivity of

digital radiographs for the detection of changes indicative

of feline DJD but to determine which of the two systems

was more sensitive. Given the superior dynamic range

afforded by digital radiographs, it is not surprising that the

digitally acquired images had similar or, for some radio-

graphic changes, higher sensitivity than analog radio-

graphs, even though analog radiographs have increased

spatial resolution. As a result, digital radiographic data

were used in the study.

The most common radiographic features of DJD were

joint-associated mineralizations for the elbow joint, tarso-

metatarsal dorsal bone proliferation, intraarticular mineral-

izations in the stifle joint and osteophytes in the coxofemoral

joint. Also, intraarticular opacity consistent with joint effu-

sion and subchondral bone erosions–cysts were not detected

often in feline joints, including those with severe cartilage

damage and subchondral bone exposure. Except for the

coxofemoral joint, osteophytes were not the most common

radiographic sign of DJD, and their severity scores were low.

Since other forms of new bone formation and joint-associ-

ated and intraarticular mineralizations were seen commonly

in feline joints with DJD, the sentiment that cats form less

new bone in association with DJD than other species should

be clarified. Based on our results, cats form periarticular new

bone, but the radiographic appearance is different to dogs.

The fact that some radiographic features not commonly seen

in dogs, such as joint-associated mineralizations and men-

iscal mineralization, were seen commonly in cats, suggests


that the radiographic signs of DJD are different in cats than

dogs. This needs further clarification.

Imaging of cartilage using radiography is impossible

since cartilage silhouettes with joint fluid and cannot be

distinguished unless mineralized. Thus, the conventional

radiographic evaluation of DJD is based on the presence of

other radiographic changes that are related with joint de-

generation. Although conventional radiographs are the

easiest indirect method to evaluate degenerative changes in

joints, little is known about the usefulness of the radio-

graphic features of osteoarthritis as predictors of articular

cartilage degeneration in humans or animals. Marginal

osteophytes were the most sensitive radiographic feature

for detection of osteoarthritis of the tibiofemoral joint in

people.14 Our results indicate that when considering all

joints, there is significant correlation between cartilage

damage and the detection of osteophytes and joint-asso-

ciated mineralizations. However, these results should in-

terpreted cautiously since this correlation was only fair

(Kendall’s t¼ 0.21–0.4). When looking at the various

joints individually, although most of the correlations were

statistically significant, only the presence of osteophytes

and the subjective radiographic DJD score had a correla-

tion above 0.4 (moderate correlation) with the presence of

cartilage damage in the elbow and coxofemoral joints. The

correlation of cartilage damage with the other radiographic

features was either fair to moderate, or not significant. This

resulted from the high numbers of joints with no radio-

graphic signs of DJD, but with cartilage lesions present.

Cautious interpretation should also be made about the

insignificant correlation between India ink retention and

radiographic dorsal new intertarsal and tarsometatarsal

bone. In this study, as an initial evaluation, the talocrural,

tarsometatarsal, and intertarsal joints were considered as a

single entity when evaluating radiographic signs of DJD.

However, cartilage damage was evaluated only in the main

and more mobile talocrural joint and not in any of the

intertarsal or tarsometatarsal joints. This likely explains the

reason why the correlation between ink retention score and

the presence of new bone formation in the intertarsal and

tarsometatarsal joints was not significant and the same

could explain the significant but slight correlation (Ken-

dall’s t¼ 0.26; P¼ 0.003) between ink score and the sub-

jective radiographic DJD score in the tarsal joint.

However, the study was designed to evaluate the radio-

graphic features of the whole joint, but to evaluate the

cartilage only in the most mobile aspect of the joint. That

the dorsal new bone does not correlate with cartilage dam-

age in the tibio-tarsal joint is clinically relevant.

It may be possible to detect various degrees of cartilage

damage radiographically using diffraction enhanced radio-

graphic imaging.20,21 High-resolution magnetic resonance

imaging (at 4T) and micro-CT can also be used to detect

cartilage lesions with a diameter 42mm, but their ability

to detect fibrillation, surface irregularities, and cracks was

poor in other studies.22

It is not surprising that cartilage fibrillation was present

in some joints before evidence of DJD was apparent

radiographically. Cartilage damage is an early change in

the process of joint degeneration and other changes, such

as osteophytosis and subchondral sclerosis, become appar-

ent radiographically only in more advanced stages of the

disease. However, based on what we observed, severe

cartilage damage with exposure of subchondral bone may

be present with only mild radiographic evidence of DJD.

There may be a mismatch between radiographic changes

of DJD and pain elicited on joint manipulation. For ex-

ample, in one evaluation, 34% of painful joints did not

have radiographic evidence of DJD.3 And, in another

comparison, only 33% of joints with radiographic signs of

DJD were painful on manipulation.8 Difficulty in assessing

pain in cats may be the cause of this mismatch. Based on

our results, the presence of moderate and severe cartilage

damage in joints with normal radiographs or mild radio-

graphic signs of DJD may explain this mismatch partially.

The greatest cartilage damage was seen in the elbow and

stifle joints, with the distribution of the lesions being con-

sistent with medial compartment disease. In other work, we

found radiographic evidence of meniscal mineralization as

a predictor of medial compartment stifle joint disease.19

This has also been suggested in guinea-pigs.23

Medial compartment elbow joint disease is recognized in

dogs24,25 and appears to be associated with medial co-

ronoid process disease, humeroulnar incongruency, and

abnormal forces acting in the medial compartment of the

joint.26–28 The cause of cartilage damage in the medial

compartment of the elbow joints in this study is unknown.

Fragmented medial coronoid process or elbow incongru-

ency have not been reported in cats, although arthroscopic-

ally detected craniomedial elbow fragments in a cat were

suggested to be from the medial coronoid process. 29 In our

study, intraarticular osteochrondral fragments were found

in some elbows with cartilage damage of the medial com-

partment, but the medial coronoid process was macro-

scopically assessed to be intact in those joints. We did not

determine the cause of medial compartment cartilage dam-

age of the feline elbow joint observed herein.

The determination of the Total Cartilage Damage Score

and the Cartilage Damage Score was based on calculating

the fraction of the total articular cartilage that was dam-

aged from digital photographs. Despite the fact that the

surfaces being measured were curved, the decision was

made to use digital photographs rather than tracings from

superimposed thin plastic film.k Tracings were inaccurate

because the thin plastic could not be adapted accurately to

the small articular surfaces and it was difficult to identify

kParafilm: Pechiney Plastic Packaging Company, Chicago, IL.


the lesions through the plastic. Digital photographs were

made at the same distance and same exact position to

minimize variance.

Therefore, based on our results, we reject the null hy-

pothesis that there is no correlation between radiographic

features of DJD and the presence of macroscopically de-

tectable articular cartilage damage in feline appendicular

joints. However, there were only fair to moderate cor-

relations between radiographic features of DJD and the

presence of macroscopic cartilage damage. The joint

most likely to have cartilage damage without radiographic

evidence of DJD is the stifle (71%) followed by the coxo-

femoral joint (57%), elbow (57%), and tarsal joint (46%).

The digital radiographic findings indicative of DJD with

the greatest association with cartilage damage were the

presence of osteophytes for the elbow (Kendall’s t¼ 0.52,

moderate correlation; Po0.0001), tarsal (Kendall’s t¼0.35, fair correlation; P¼ 0.0001), coxofemoral joints

(Kendall’s t¼ 0.43, moderate correlation; Po0.0001),

and intraarticular mineralizations for the stifle joint

(Kendall’s t¼ 0.32, fair correlation; P¼ 0.0003).

ACKNOWLEDGMENTS

This study was funded by Novartis Animal Health, through theircompetitive grants program. The authors have no financial or personalrelationships that could possibly influence or inappropriately bias thiswork.

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3. Clarke SP, Bennett D. Feline osteoarthritis: a prospective study of 28cases. J Small Anim Pract 2006;47:439–445.

4. Godfrey DR. Osteoarthritis in cats: a retrospective radiological study.J Small Anim Pract 2005;46:425–429.

5. Lascelles BD, Henry JB, Brown J, et al. Cross-sectional study eval-uating the prevalence of radiographic degenerative joint disease in domes-ticated cats. Vet Surg 2010;39:535–544.

6. Lascelles BD. Feline degenerative joint disease. Vet Surg 2010;39:2–13.7. Gunew MN, Menrath VH, Marshall RD. Long-term safety, efficacy

and palatability of oral meloxicam at 0.01–0.03mg/kg for treatment ofosteoarthritic pain in cats. J Feline Med Surg 2008;10:235–241.

8. Lascelles BD, Hansen BD, Roe S, et al. Evaluation of client-specificoutcome measures and activity monitoring to measure pain relief in cats withosteoarthritis. J Vet Intern Med 2007;21:410–416.

9. Lascelles BD, Depuy V, Thomson A, et al. Evaluation of a therapeuticdiet for feline degenerative joint disease. J Vet Intern Med 2010; 24:487–495.

10. Allan GS. Radiographic features of feline joint diseases. Vet ClinN Am Small Anim Pract 2000;30:281–302.

11. Lascelles BD, Henderson AJ, Hackett IJ. Evaluation of the clinicalefficacy of meloxicam in cats with painful locomotor disorders. J Small AnimPract 2001;42:587–593.

12. Bennett D, Morton C. A study of owner observed behavioural andlifestyle changes in cats with musculoskeletal disease before and after an-algesic therapy. J Feline Med Surg 2009;11:997–1004.

13. Kijowski R, Blankenbaker DG, Stanton PT, Fine JP, De Smet AA.Radiographic findings of osteoarthritis versus arthroscopic findings of ar-ticular cartilage degeneration in the tibiofemoral joint. Radiology2006;239:818–824.

14. Kijowski R, Blankenbaker D, Stanton P, Fine J, De Smet A. Cor-relation between radiographic findings of osteoarthritis and arthroscopicfindings of articular cartilage degeneration within the patellofemoral joint.Skeletal Radiol 2006;35:895–902.

15. Bushberg JT, Seibert JA, Leidholdt EM Jr, Boone JM. Digital ra-diography. In Wilkins LW (ed): The Essential Physics of Medical Imaging.Philadelphia: Williams & Wilkins, 2002;293–316.

16. Cake MA, Read RA, Guillou B, Ghosh P. Modification of articularcartilage and subchondral bone pathology in an ovine meniscectomy modelof osteoarthritis by avocado and soya unsaponifiables (ASU). OsteoarthritisCartilage 2000;8:404–411.

17. Meachim G. Light microscopy of Indian ink preparations of fib-rillated cartilage. Ann Rheum Dis 1972;31:457–464.

18. Yoshioka M, Coutts RD, Amiel D, Hacker SA. Characterization ofa model of osteoarthritis in the rabbit knee. Osteoarthritis Cartilage1996;4:87–98.

19. Freire M, Brown J, Robertson ID, et al. Meniscal mineralization indomestic cats. Vet Surg 2010;39:545–552.

20. Muehleman C, Li J, Zhong Z. Preliminary study on diffraction en-hanced radiographic imaging for a canine model of cartilage damage.Osteoarthritis Cartilage 2006;14:882–888.

21. Muehleman C, Chapman LD, Kuettner KE, et al. Radiography ofrabbit articular cartilage with diffraction-enhanced imaging. Anat Rec ADiscov Mol Cell Evol Biol 2003;272:392–397.

22. Batiste DL, Kirkley A, Laverty S, et al. High-resolutionMRI and micro-CT in an ex vivo rabbit anterior cruciate ligamenttransection model of osteoarthritis. Osteoarthritis Cartilage 2004;12:614–626.

23. Kapadia RD, Badger AM, Levin JM, et al. Meniscal ossification inspontaneous osteoarthritis in the guinea-pig. Osteoarthritis Cartilage2000;8:374–377.

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25. Fitzpatrick N, Yeadon R, Smith T, Schulz K. Techniques of appli-cation and initial clinical experience with sliding humeral osteotomy fortreatment of medial compartment disease of the canine elbow. Vet Surg2009;38:261–278.

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27. Fitzpatrick N, Smith TJ, Evans RB, Yeadon R. Radiographic andarthroscopic findings in the elbow joints of 263 dogs with medial coronoiddisease. Vet Surg 2009;38:213–223.

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69

pUBLICATION 3

Meniscal Mineralization in Domestic Cats. Freire M, Brown J, Robertson ID,

Pease AP, Hash J, Hunter S, Simpson W, Thomson Sumrell A, Lascelles BD.

Veterinary Surgery. 2010;39(5):545-52.



Meniscal Mineralization in Domestic Cats

Mila Freire1, DVM, James Brown2, DVM, Diplomate ACVR, Ian D. Robertson2, BVSc Diplomate ACVR,Anthony P. Pease2, DVM, MS, Diplomate ACVR, Jonathan Hash1, BA, Stuart Hunter3, DVM, DiplomateACVP, Wendy Simpson4, DVM, Andrea Thomson Sumrell1, RVT, and B. Duncan X. Lascelles1, BSc, BVSc,PhD, DSAS(ST), Diplomate ACVS & ECVS1Comparative Pain Research Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 2Department of Molecular

Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 3Department of Population Health and

Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 4Morrisville Cat Hospital, Morrisville, NC

Corresponding author

B. Duncan X. Lascelles, BSc, BVSc, PhD,

DSAS(ST), Diplomate ACVS & ECVS,

Comparative Pain Research Laboratory and

Surgery Section, Department of Clinical

Sciences, North Carolina State University,

4700 Hillsborough Street, Raleigh, NC

27606

E-mail: [email protected]

Submitted May 2009; Accepted August 2009

DOI:10.1111/j.1532-950X.2010.00648.x

Objective: To (1) determine prevalence of radiographically detectable meniscalmineralization in domestic cats and (2) to evaluate the association between men-iscal mineralization and degenerative joint disease (DJD).Study Design: Prospective study.Animals: Client-owned cats (n=100) and 30 feline cadavers.Methods: Randomly selected client-owned cats were used to determine the prev-alence of meniscal mineralization. Stifles from feline cadavers were used to eval-uate the relationship between meniscal mineralization (using high-resolutionX-ray), radiographic DJD, and cartilage damage. Menisci were evaluatedhistologically.Results: Forty-six percent of the client-owned cats had meniscal mineralizationdetected in 1 or both stifles. Pain scores were not significantly different betweenstifles with meniscal mineralization and those with no radiographic pathology(P=.38). Thirty-four of 57 cadaver stifles had meniscal mineralization, whichwas always located in the cranial horn of the medial meniscus. Percentage miner-alization of the menisci was significantly correlated with the cartilage damagescore of the medial femoral (r2=0.6; Po .0001) and tibial (r2=0.5; Po .0001)condyles as well as with the total joint cartilage damage (r2=0.36; Po .0001)score and DJD score (r2=0.8; Po .0001).Conclusion: Meniscal mineralization is a common condition in domestic cats andseems to indicate medial compartment DJD.Clinical Relevance: Clinical significance of meniscal mineralization is uncertain.Further work is needed to determine if the meniscal mineralization is a cause, or aconsequence of joint degeneration.

Meniscal mineralization is a poorly understood conditionthat has been reported in reptiles, rodents, birds, nondo-mestic cats, and nonhuman primates.1–4 Although de-scribed in people, it is considered a rare condition5–12 andthere have been a few case reports in dogs and domesticcats.1,13,14

The cause of meniscal mineralization (meniscal ossifi-cation1,2,11–15; meniscal ossicles6–11,16; meniscal calcifica-tion1,5,13) is unknown. Developmental (phylogenetic) andposttraumatic causes have been suggested in peo-ple.6,7,10,12 The phylogenetic theory suggests that meniscalmineralization represents a congenital vestigial struc-ture that should be interpreted as a variant of normal

anatomy.6,7 The posttraumatic theory asserts that men-iscal mineralization is acquired by degeneration or met-aplasia after isolated or recurrent trauma.7 It has beensuggested that meniscal mineralization is a normal ana-tomic feature in nondomestic cats,2 a primary vestigialanomaly in dogs and cats,1,14 and to occur secondary totrauma or in association with cranial cruciate ligamentrupture in dogs and cats.1,13

The frequency of occurrence of meniscal mineraliza-tion in domestic cats is unknown. It is also unknown ifmeniscal mineralization is associated with joint pain orlameness or if meniscal mineralization is associated withdegeneration of joint tissues such as cartilage.

Our purpose was to determine prevalence of radio-graphically detectable meniscal mineralization in domesticcats. We hypothesized that the prevalence was high(4 30%) and further, that meniscal mineralization is

Study was funded by a grant from Novartis Animal Health

through their global Fellowship Research Program



associated with degenerative joint disease (DJD), as indi-cated by cartilage degeneration.

MATERIALS AND METHODS

We conducted a prospective, observational study. Part Iestablished the prevalence of radiographically detectablemeniscal mineralization in domestic cats and part II eval-uated the relationship between meniscal mineralization andDJD measured by cartilage damage.

Cats

Prevalence Study. A population of 100 client-owned catsrandomly selected from the client database of MorrisvilleCat Hospital (Morrisville, NC) was used to determine theprevalence of radiographically detectable meniscal miner-alization.

Cadaver Study. Thirty adult cats euthanatized (populationcontrol) at a county animal shelter were studied. We aimedto recruit 30 cats of any age, equally distributed betweencases with and without radiographically detectable men-iscal mineralization, with no other detectable stifle pathol-ogy.

Prevalence Study

Using a database of 1640 cats from a single veterinarypractice, a population of 100 cats was randomly selectedfor study. To achieve this, the cats in the database were di-vided into 4 age groups (0–5; 5–10; 10–15; and 15–20 yearsold). Cats that were exactly 5, 10, or 15 years old were as-signed to the 6 months–5 years, 5–10 years, and 10–15

years groups, respectively. Within each age group, each catwas assigned a unique number, and then the cats in eachgroup were randomly ranked using computer software.The first 25 cats in each group whose owners were willing toparticipate in the study were included. Once selected, eachcat was evaluated, sedated, and orthogonal radiographicprojections of the stifle joints taken using an indirect digitalflat panel imaging system (CanonMedical CXDI-50G Sen-sor, Eklin Medical Systems, Santa Clara, CA).

Digital radiographs made were evaluated by 2 boardcertified radiologists (A.P., J.B.) and a board certified sur-geon (B.D.X.L.) for radiographically detectable pathologyincluding meniscal mineralization. Digital radiographswere viewed (Dell Ultra-sharp 2407WFP color monitors,24’’ LCD resolution of 1920� 1200) and standard medicalimage viewing software (eFilm 2.1.2, Merge Healthcare,Milwaukee, WI). Radiologic features considered indicativeof presence of DJD were: joint effusion, osteophytes, en-thesiophytes, joint associated mineralization, sclerosis,subchondral bone erosions-cysts, and presence of intra-articular mineralizations. Meniscal mineralization wasconsidered under intra-articular mineralization as a miner-alization detected in the intra-articular space, and whichappeared to be located within the area of the lateral or me-dial menisci in both craniocaudal and mediolateral projec-tions of the stifle (Fig 1). A scale (0–4) was used for gradingof severity of each of the radiographic changes identified(0=normal; 1= trivial; 2=mild; 3=moderate; 4= se-vere). A subjective radiographic DJD score (0–10) where0=no radiographic abnormalities identified and 10=an-kylosis, was assigned to each stifle based on the presence ofradiographic change and its severity. Age, weight, bodycondition score (BCS; http://www.ivis.org/journals/vetfocus/16_1/en/7.pdf), breed, and sex of the cats were re-corded. During orthopedic evaluation, the response to

Figure 1 The severity of radiographically detectable meniscal mineralization was graded using a scale from 0–4 (0 = normal; 1 = trivial; 2 = mild;

3 = moderate; 4 = severe). The stifle digital radiographs from cadaver specimens show meniscal mineralizations graded as trivial (A), moderate (B), and

severe (C).


Freire et alMeniscal Mineralization in Cats

http://www.ivis.org/journals/vetfocus/16_1/en/7.pdf

http://www.ivis.org/journals/vetfocus/16_1/en/7.pdf

palpation of every joint and part of the axial skeleton wasgraded: 0=no resentment; 1=mild withdrawal, mildlyresists; 2=moderate withdrawal, body tenses, may orientto site, may vocalize, increase in vocalization; 3=orientsto site, forcible withdrawal from manipulation, may vocal-ize or hiss or bite; and 4= tries to escape, prevent manip-ulation, bite/hiss, marked guarding of area.

Cadaver Study

After euthanasia, body weight and BCS were recorded andan orthopedic examination of each stifle joint was per-formed. Only cats without grossly detectable stifle pathol-ogy (cranial cruciate ligament rupture, patella luxation)were included in the study. The presence of grade I patellaluxation was considered acceptable. Orthogonal radio-graphs of the cadaver stifle joints were acquired using adigital imaging system (described above) and also with ahigh detail film/screen system (Kodak Lanex Fine screens,Carestream Health, Rochester, NY; Super HR-U � 30 rayfilm, Fuji Medical Systems, Stamford, CT). Both digitaland analog radiographs were evaluated blindly by the sameboard certified veterinary radiologists and surgeon to de-termine radiographic scores based on the features de-scribed earlier.

Morphologic Examination. Stifle joints were carefullyopened to avoid damage to any cartilage surfaces for grossobservation.Menisci were dissected from their attachmentsand retained for evaluation. The surface appearance of thejoints was studied for fibrillation and/or erosion of the ar-ticular cartilage using India ink application.17 The cartilagesurface was painted with India ink twice, rinsing the carti-lage with water each time, 3 minutes after the ink was ap-plied. The severity of surface damage of the articularcartilage was scored based on ink retention, and graded18:grade 1= intact surface: surface appears normal and doesnot retain any ink; grade 2=minimal fibrillation: site ap-pears normal before staining, but retains India ink as elon-gated specks or light gray patches; grade 3=overtfibrillation: the cartilage is velvety in appearance and re-tains ink as intense black patches; and grade 4=erosion:loss of cartilage exposing the underlying bone.

The severity of articular cartilage damage present in eachstifle joint was expressed as the total cartilage damage score(TCDS) calculated from the addition of the cartilage dam-age score (CDS) of 6 articular areas: medial and lateralfemoral condyles, medial, and lateral tibial condyles, pa-tella and femoral trochlea. CDS of each of those areas wascalculated as the percent of the total articular cartilage areadamaged, multiplied by the degree of cartilage damagebased on the ink retention grading system. CDS valueranged from 0 to 400 (0=no cartilage damage;400=complete exposure of subchondral bone over thewhole of the articular surface of that bone). TCDS andCDS were calculated using the following equations:

CDS ¼ ½%area1 � ink gradearea1� þ ½%area2 � ink gradearea2�

TCDS ¼ CDSlat fem condyle þ CDSmed fem condyle

þ CDSlat tibial condyle þ CDSmed tibial condyle

þ CDSpatella þ CDSfemoral trochlea

TCDS value ranged from 0 to 2400 (0=no cartilagedamage present; 2400=complete exposure of subchondralbone over all articular surfaces).

To calculate CDS and TCDS, digital photographs of thefemoral condyles, femoral trochlea, tibial plateau, and pa-tella, after the application of the India ink, were made byphotographing these surfaces in exactly the same way eachtime. Computer software (Adobe Photoshop 7.0, Adobe,San Jose, CA) was used to calculate the percent of the car-tilage area retaining India ink as a result of cartilage fibril-lation. Despite the fact that some of the surfaces beingmeasured were curved, pilot work established that the useof X-ray film or thin plastic compared with digital photo-graphs to measure damaged areas resulted in significantlygreater variance, and small areas of cartilage damage weredifficult to define through the plastic.

Imaging. High detail radiographs (Faxitron X-Ray sys-tem, Fuji Medical X-Ray Film; Super HR-U 30; Fujifilm;Stamford, CT; 30 kV, 40 seconds) of menisci from the stiflejoints were evaluated looking for presence of meniscal min-eralization. Location and number of discrete areas of min-eralization were described. High detail radiographic imageswere digitized (1.500 by 300 radiographs photographed usingNikon D2� 10MP 35mm digital camera, producing im-ages of 4288� 2848 pixels) and using computer software(Adobe Photoshop 7.0) the calcified area of the meniscuswas calculated and expressed as a percent of the total areaof the meniscus (%MinFAX).

Microscopy. Harvested menisci were fixed in 10% forma-lin for 48 hours. Menisci that could not be cut were decal-cified in formic acid solution for 24–48 hours. Afterfixation and decalcification, menisci were divided into 3with 2 cuts oriented radially to the peripheral margin of themeniscus, creating cranial, middle, and caudal sections.Meniscal segments were sectioned, stained with hem-atoxylin and eosin and evaluated histologically. In everycase with radiographically detectable mineralization, sec-tioning was continued until the area of mineralization wasidentified histologically.

Statistical Analysis

Descriptive statistics were used to describe the prevalenceof meniscal mineralization in the clinical population. Catswith no radiographic stifle pathology and those with onlymeniscal mineralization were compared for age, weight,BCS, and sex of cat, using t-tests, w2-tests, andKruskal–Wallis tests. Individual stifles with no radio-graphic stifle pathology and those with only meniscal


Freire et al Meniscal Mineralization in Cats

mineralization were compared for pain on manipulationusing a Kruskal–Wallis test.

For the cadaver study, using %MinFAX as the goldstandard for the detection of meniscal mineralization, thesensitivity and specificity of digital and (traditional) analoghigh-detail film/screen radiographs were calculated. Sub-jective total DJD scores between stifles with and withoutmeniscal mineralization were compared using theKruskal–Wallis test. Nonpaired t-tests were used to com-pare TCDS and CDS between stifles with and withoutmeniscal mineralization. A correlation coefficient was cal-culated to describe the relationship between the %MinFAX

and CDS and TCDS of the joint surfaces, as well as withthe subjective total DJD score. Values of Po .05 were con-sidered significant.

RESULTS

Prevalence Study

Twenty-five cats in each age group were successfully re-cruited and studied; 18 were pure-bred and 82 were domes-tic short or long hair. There were 40 male castrated (MC)and 60 female spayed (FS). Mean (�SD) age was9.42� 5.05 years and mean weight was 5.12� 1.63 kg(range, 2.08–10.16 kg).

Forty-six cats had meniscal mineralization detected inone or both stifles (27 cats bilateral, 19 cats unilateral). Inthose cats with unilateral meniscal mineralization, the rightstifle was affected in 10 and the left stifle in 9 cats. Cats withmeniscal mineralization were 17 castrated males and 29spayed females with a mean age of 10.70� 4.73 years andmean weight of 4.92� 1.57 kg. Fifty-four cats (54%; 17castrated males, 31 spayed females; mean age, 8.33� 5.13years; mean weight, 5.80� 1.7 kg) had no meniscal miner-alization detected on digital radiographs. Of 100 cats eval-uated, 21 (21%) had meniscal mineralization as the onlyradiographic change detected on digital radiographs of thestifles, and 36 cats (36%) had no radiographic signs indica-tive of any stifle pathology. Cats with meniscal mineraliza-tion were significantly older (10.50� 5.2 years; P=.027),weighed significantly less (4.57� 1.46 kg; P=.043) andwere of significantly lower BCS (median, 2; range, 1–5;

P=.039) than those with no radiographic stifle pathology(age, 7.46� 4.64 years; weight, 5.50� 1.71 kg; medianBCS, 3 [range, 2–5]).

Of 200 stifles evaluated, 73 (37%) had meniscal miner-alization identified on digital radiographs. Of the affectedstifles, 54 (27% of all stifles) had no other radiographicsigns of DJD besides meniscal mineralization. There wasno significant difference between the pain scores for stifleswith no radiographic pathology and those with only men-iscal mineralization (P=.38).

Cadaver Study

Of 30 cats, 3 stifles were excluded: 1 because intra-articularmineralization other than meniscal mineralization wasidentified in both stifles (the origin of those mineralizationscould not be determined on macroscopic examination) and1 cat had a cranial cruciate ligament rupture in the rightstifle. Thus, 57 stifles from 29 cats were included in theanalysis. Breeds were domestic short hair (23), domesticmedium hair (2), domestic long hair (2), Main Coon (1),and Himalayan (1). There were 6 spayed females, 13 fe-males, 8 castrated males, and 2 males. Mean (� SD) age ofthe cats was 9.91� 4.61 years, mean weight was4.8� 1.33 kg, and median BCS was 3 (range, 2–5). No sig-nificant differences were found in age (P=.15), weight(P=.44), and BCS (P=.61) between cats with and with-out meniscal mineralization.

Meniscal mineralization was detected on high detailradiographs of medial and lateral menisci in 34 of 57 stifles(60%). Mineralization was located in the cranial horn ofthe medial meniscus in all instances and partially involvedthe cranial intermeniscal ligament in 3 stifles. Sixteen catshad bilateral (left and right stifle medial meniscus) miner-alization, 1 cat had unilateral meniscal mineralization, 1cat had bilateral meniscal mineralization but the right stiflewas not included because of cranial cruciate ligament rup-ture, and 11 cats had no meniscal mineralization in eitherstifle. Mineralization was confined to a single area in 13(38%) menisci and multiple areas in 21 (62%) menisci. Inmenisci with mineralization, %MinFAX had a mean (�SD)value of 7.83� 11.22% of the total area of the meniscus(range, 1.5–55%; Fig 2). Digital radiographs had a

Figure 2 Mineralization of the cranial horn of the medial meniscus (left) on a cadaver specimen detected on high detail (Faxitron) radiographs (A)

Severity of meniscal mineralization based on digital radiographs of this cadaver specimen was graded as trivial. Articular surface of the distal femur of

the same specimen shows the difference in cartilage fibrillation and erosion of the medial (left) and lateral (right) femoral condyles after the application

of India ink (B).



sensitivity and specificity of 91% and 100%, respectively,for detection of meniscal mineralization. Analog high de-tail film/screen radiographs had a sensitivity and specificityof 88% and 100%, respectively, for detection of meniscalmineralization.

Significant differences were found for subjective totalDJD scores assigned from digital (median 1; range 0–5)and analog high detail film/screen radiographs (median 1;range 0–4; P=.021). The largest paired difference was 1,occurring in 8 of 57 stifles and in 3 stifles a score of 0 wasassigned for the analog films, and 1 for the digital images.The subjective total DJD score from digital images wassignificantly different between stifles with meniscal miner-alization (median, 1; range, 0–5) and without meniscalmineralization (median, 0; range, 0–1; Po .001).

Gross Morphologic Findings

The TCDS of the 57 stifles evaluated had a mean (�SD)value of 51� 92. CDS mean value for the 6 articular sur-faces in the stifle joint were: medial femoral condyle27� 42; lateral femoral condyle 3.8� 7.5; femoral trochlea8.7� 15; medial tibial condyle 12� 24; lateral tibial con-dyle 2.6� 5.7; and patella 27� 32. The Ink score represent-ing the worse cartilage damage in each stifle joint had amedian value of 2 (range, 1–4). The TCDS was significantlydifferent between stifles with meniscal mineralization(104� 103) and stifles without meniscal mineralization(50.5� 62.2; P=.028).

In stifles with mineralization of the menisci, CDS wassignificantly different when comparing medial (40.4� 48.9)and lateral (3.91� 6.33) femoral condyles (P=.0001), andmedial (15.5� 29.0) and lateral (2.81� 6.42) tibial condyles(P=.01). In stifles without meniscal mineralization no sig-nificant differences were found in CDS when comparingmedial (8.97� 16.8) and lateral (3.80� 9.05) femoral con-dyles (P=.22); however, CDS was significantly differentfor medial (8.70� 12.6) and lateral (2.21� 4.39) tibial con-dyles (P=.009).

Meniscal Mineralization and CDS Correlation

The percent area of the menisci taken up by the meniscalmineralization was significantly correlated with the CDS ofmedial femoral and medial tibial condyles as well as with

the TCDS and subjective total DJD score (Po .05). Thiscorrelation was good with the medial femoral condyle(r2=0.6; Po .0001), moderate with the medial tibial con-dyle (r2=0.5; Po .0001), fair with the TCDS (r2=0.36;Po .0001) and very good with the subjective total DJDscore (r2=0.8; Po .0001). No significant correlation wasfound between the percent of the menisci taken up by themeniscal mineralization and the CDS of the lateral femoralor tibial condyles, patella or femoral trochlea (P4 .05).

Meniscal Histopathology

Meniscal mineralization was identified histologically in allthe menisci in which mineralization was detected on highdetail radiographs. Histopathologically, 14 menisci (41%of all the mineralized menisci), had intrameniscal ossifica-tion consisting of cancellous bone and bone marrow struc-ture, and metaplasia of the fibrocartilage surrounding theossified area (Fig 3). Twenty menisci (59% of all the min-eralized menisci) showed intrameniscal mineralizationsconsisting of areas of chondro-osseous metaplasia of thefibrocartilage with no organized structure. No abnormali-ties were detected histopathologically in any of the lateralmenisci (Fig 3).

DISCUSSION

Our results indicate that meniscal mineralization is a com-mon feature detected on conventional orthogonal radio-graphs of the stifle in domestic cats. In a population of 100cats selected from a database of a single practice, meniscalmineralization was identified in 37% of the stifles radio-graphed. Although the cats in the clinical study did nothave the presence of meniscal mineralization confirmed byimaging of the menisci, or by histopathology, when thesame features were observed in the cadaver study, meniscalcalcification was found in every instance. Additionally, wefound it relatively easy to find cats with meniscal mineral-ization for the cadaveric study although we do not knowthe prevalence of meniscal mineralization in this popula-tion of cats. Walker et al16 described meniscal mineraliza-tion to be radiographically evident in 8 of 12 African lionsand 6 of 7 Bengal and Bengal-cross tigers (all except 1were 4 1 year of age), but their study did not establish the

Figure 3 Histology of meniscal mineralization and ossification. Meniscal mineralization appeared as areas of chondro-osseous metaplasia (A) or as

organized structures with cancellous bone and bone marrow, surrounded by metaplasia of the fibrocartilage (B, C, and D). Hematoxylin and eosin stain

(A, B, C � 5; D � 10).



prevalence of meniscal mineralization in these species.Meniscal mineralization has been reported in dogs13,14 butthe prevalence in the canine population is unknown. In hu-mans, regional mineralization of the knee meniscus is a rarefinding with an incidence of 0.15% according to a studywhere 1287 patients were evaluated with magnetic reso-nance imaging.10 Approximately 50 cases of human men-iscal mineralization have been reported, mainly in casereports.6–12,19

Compared with cats with no radiographically visiblepathology, cats with suspected meniscal mineralizationand no other radiographic lesions were significantlyolder, weighed less, and had a lower BCS. If meniscal min-eralization is associated with DJD, then these associationslikely represent an association between age and DJD. It isknown that cats tend to lose weight and BCS as they getolder.20–22

Quantifying meniscal mineralization and investigatingthe relationship to DJD has not been reported in cats, dogs,or humans. Kapadia et al15 reported the volume of men-iscal mineralization in the menisci of 2 age groups (6 and 24month old) of guinea-pigs using micro-computed tomog-raphy. In both age groups, the ossified region of the medialmeniscus was significantly larger than the lateral meniscus.The volume of the medial meniscal mineralization in-creased significantly between 6 and 24 months of age, andthe medial compartment of the stifle had more new boneformation, which was also associated with increasing age.It was suggested that the bone remodeling and cartilagedegeneration evident in the medial compartment of the sti-fle joint could be a consequence of the presence of ossifica-tion of the medial meniscus which might have altered the

joint biomechanics and, in part, initiated medial compart-ment joint degeneration. The authors suggested that men-iscal mineralization in guinea-pigs, being a model ofosteoarthritis (OA), could offer insights into the role ofthe meniscus in the development of OA in humans as well.The present study, showed a clear relationship betweenmeniscal mineralization and cartilage damage on the me-dial femoral condyle and medial tibial plateau. However, itis not known if the meniscal mineralization is a cause, orresult of the cartilage damage. The fact that there was morecartilage damage on the medial tibial plateau comparedwith the lateral tibial plateau in the normal stifles mightsuggest that meniscal mineralization is a response to de-generative changes.

As with Kapadia et al,15 our results suggest that men-iscal mineralization may be associated with medial com-partment joint disease of the stifle joint in cats. In people,medial compartment DJD of the knee has been associatedwith high adduction moment at the knee during ambula-tion.23–27 It may be that gait patterns, alteration of gaitpatterns, or pelvic limb conformation in some cats maypredispose to meniscal mineralization, and this may inturn hasten the progression of DJD. This of course isspeculative, but further investigation of the condition incats may help in preventing the disease in this species, andmay reveal a naturally occurring model of medial com-partment pathology that could be used to study the dis-ease in people.

The high correlation (r2=0.8; Po .0001) between thepercent of the area of the menisci taken up by the meniscalmineralization and subjective total DJD score should beinterpreted cautiously since meniscal mineralization was

Figure 4 Articular surface of the distal femur of a cadaver specimen showing a distinct groove in the medial femoral condyle (left) (A). Note the

retention of India ink by the medial condyle because of fibrillation and erosion of the articular cartilage (B). Appearance of the lateral (right) and medial

(left) menisci of the same cadaver specimen (C). Note the normal size of the lateral menisci, compared with the irregularly shaped and enlarged medial

menisci. High detail (Faxitron) radiographs showed mineralization of the medial menisci (D) (43% of the total area of the medial meniscus is taken up by

the mineralization).



one of the radiographic features considered indicative ofDJD and its detection on radiographs contributed directlyto increase the total DJD score. The case with the largestmeniscal mineralization we describe (55% of the total areaof the meniscus) had a distinct groove in the medial femoralcondyle and it appeared the mineralization of the medialmeniscus had been articulating with the femur (Fig 4). Aprevious study also reported the presence of a groove in themedial femoral condyle that articulated with an ossicle ofthe medial meniscus in the stifle joint of a tiger (Panteratigris).2 In that report, the authors suggested that theossicles within the medial meniscus were a normal adaptiveanatomic feature that helped distribution of load throughthe meniscus thereby reducing wear and fatigue of the ar-ticular surfaces of the femur and tibia. In contrast to this,we consider the changes in the medial femoral condyle tobe degenerative, likely in response, at least in part, to thepresence of the meniscal mineralization.

The cause of meniscal ossification is debated. Ourhistologic findings seem to suggest that menisci undergo aprocess of ossification, starting with a chondro-osseoustransformation of the fibrocartilage with mineral deposi-tion, ultimately organizing into cancellous bone and bonemarrow structure. That the ossified areas continue to growby conversion of fibrocartilage to bone is suggested by thepresence of chondro-osseous metaplasia of the fibrocarti-lage observed in the periphery of the ossified area. Thebilateral symmetrical appearance of the meniscal mineral-izations could support a nondegenerative origin, however,repetitive microtrauma because of bilateral gait abnormal-ities, or pelvic limb conformation in some cats could triggerthe degenerative transformation at specific areas of themenisci bilaterally. In people, chondrocalcinosis of themeniscus has been associated with several distinct meta-bolic disorders including hemochromatosis, hyper-parathyroidism, and hypothyroidism.28 The associationbetween metabolic disorders and mineralization of menisciin cats is unknown.

The clinical significance of the presence of meniscalmineralization in domestic cat menisci is unknown. Indeed,our study showed no difference in pain scores between ra-diographically normal stifles and those with just meniscalmineralization. However, despite all the assessments beingperformed by a single individual, musculoskeletal pain isdifficult to assess in cats. Further work might look at suchgroups of cats and make the evaluations before and afterthe administration of a known analgesic.

Using high detail (Faxitron) radiographs as a goldstandard for detection of meniscal mineralization, digitalradiographs and analog high detail film/screen radiographswere 100% specific and had a high sensitivity for detectionof meniscal mineralization (91% and 88%, respectively).Both radiographic techniques are considered acceptablefor detection of meniscal mineralization in cats, althoughsome of the smaller areas of mineralization may be missedwith both techniques. Given the superior dynamic rangeafforded by digital imaging, it is not surprising that thedigitally acquired images had higher sensitivity.

One criticism of our study is the use of digital imagesto make measures of cartilage damage. Pilot work using X-ray film and thin plastic or flexible film (parafilm: PechineyPlastic Packaging Company, Chicago, IL) indicated thatthe results from using flexible film had a higher coefficientof variation, the lesions in the cartilage were difficult to seethrough the parafilm, it was very difficult to delineatethe lesions with a marker and the flexible film was impos-sible to place around some surfaces. Measures taken fromdigital photographs of the articular surface itself, despitebeing two-dimensional were considered to be more accu-rate and feasible to be performed for all the surfaces. Ad-ditionally, our study was a comparative study of the stifleswith and without meniscal mineralization.

Little is known about the origin of meniscal mineral-izations in the feline menisci as well as in other species,and the clinical significance of radiographically detectedmeniscal mineralization is uncertain. However, the pres-ence of meniscal mineralizations is a common condition indomestic cats and seems to indicate medial compartmentjoint disease. Further work to characterize this phenome-non and its role in the development of DJD in cats is re-quired. A better understanding of this phenomenon in catscould help to understand this process in people and otheranimals.

REFERENCES

1. Whiting PG, Pool RR: Intrameniscal calcification andossification in the stifle joints of three domestic cats. J AmAnim Hosp Assoc 1985;21:579–584

2. Ganey TM, Ogden JA, Abou-Madi N, et al: Meniscalossification. II the normal pattern in the tiger knee. SkeletalRadiol 1994;23:173–179

3. Kirberger RM, Groenewald HB, Wagner WM: Aradiological study of the sesamoid bones and os meniscus ofthe cheetah (Acinonyx jubatus). Vet Comp Orthop Traumatol2000;13:172–177

4. Pedersen HE: The ossicles of the semilunar cartilages ofrodents. Anat Rec 1949;105:1–7

5. Noble J, Hamblen DL: The pathology of the degeneratemeniscus lesion. J Bone Jt Surg 1975;2:180–186

6. Rosen IE: Unusual intrameniscal lunulae. J Bone Jt Surg1958;4:925–928

7. Liu SH, Osti L, Raskin A, et al: Meniscal ossicles: two casereports and a review of the literature. Arthroscopy1994;10:296–298

8. Yoo JH, Yang BK, Son BK: Meniscal ossicle: a case report.The Knee 2007;14:493–496

9. Schaefer WD, Martin DF, Pope TL, et al: Meniscal ossicle.J Southern Orthop Assoc 1996;5:126–129

10. Schnarkowski P, Tirman FJ, Fuchigami KD, et al: Meniscalossicle: radiographic and MR imaging findings. Radiology1995;196:47–50

11. Kato Y, Oshida M, Saito A, et al: Meniscal ossicles. J OrthopSci 2007;12:375–380



12. Ogden JL, Ganey TM, Arrington JA, et al: Meniscal

ossification. I Human. Skeletal Radiol 1994;23:167–172

13. Reinke J, Mughannam A: Meniscal calcification and

ossification in six cats and two dogs. J Am Anim Hosp Assoc

1994;30:145–152

14. Weber NA: Apparent primary ossification of the menisci in a

dog. J Am Vet Med Assoc 1998;212:1892–1894

15. Kapadia RD, Badger AM, Levin JM, et al: Meniscal

ossification in spontaneous osteoarthritis in the guinea-pig.

Osteoarthritis Cartilage 2000;8:374–377

16. Walker M, Phalan D, Jensen J, et al: Meniscal ossicles in large

non-domestic cats. Vet Radiol Ultrasound 2002;43:249–254

17. Meachim G: Light microscopy of Indian ink preparations of

fibrillated cartilage. Ann Rheum Dis 1972;31:457–464

18. YoshiokaM, Courtts RD, Amiel D, et al: Characterization of

a model of osteoarthritis in the rabbit knee. Osteoarthritis

Cartilage 1996;4:87–98

19. Le Minor JM, Kempf JF: Ossicule intrameniscal du genou

(lunula): a propos d’un cas. Revue de la literature.Rev de Chir

Orthop 1989;75:501–505

20. Lund EM, Armstrong PJ, Kirk CA, et al: Prevalence and risk

factors for obesity in adult cats from private US veterinary

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21. Laflamme DP: Nutrition for aging cats and dogs and theimportance of body condition. Vet Clin Small Anim Pract2005;35:713–742

22. Kronfeld DS, Donoghue S, Glickman T: Body condition ofCats. J Nutrition 1994;124:2683–2684

23. Guo M, Axe MJ, Manal K: The influence of foot progressionangle on the knee adduction moment during walking and stairclimbing in pain free individuals with knee osteoarthritis. GaitPosture 2007;26:436–441

24. Hunt MA, Birmingham TB, Bryant D, et al: Lateraltrunk lean explains variation in dynamic knee jointload in patients with medial compartment kneeosteoarthritis. Osteoarthritis Cartilage 2008;16:591–599

25. Hurwitz DE, Sumner DR, Adriacchi TP, et al: Dynamic kneeloads during gait predict proximal tibial bone distribution.J Biomech 1998;31:423–430

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27. Zhao D, Banks SA, Mitchell KH, et al: Correlation betweenthe knee adduction torque and medial contact force for avariety of gait patterns. J Orthop Res 2007;25:789–797

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79

PUBLICATION 4

Pathology of articular cartilage and synovial membrane from elbow joints with and

without degenerative joint disease in domestic cats. M Freire, D Meuten, BDX

Lascelles. Veterinary Pathology. 2014 Jan 29. [Epub ahead of print].



Article

Pathology of Articular Cartilage andSynovial Membrane From Elbow JointsWith and Without Degenerative JointDisease in Domestic Cats

M. Freire1, D. Meuten2, and D. Lascelles1,3,4

AbstractThe elbow joint is one of the feline appendicular joints most commonly and severely affected by degenerative joint disease. Themacroscopic and histopathological lesions of the elbow joints of 30 adult cats were evaluated immediately after euthanasia.Macroscopic evidence of degenerative joint disease was found in 22 of 30 cats (39 elbow joints) (73.33% cats; 65% elbow joints),and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of the hyaline cartilage with exposure of thesubchondral bone. Distribution of the lesions in the cartilage indicated the presence of medial compartment joint disease (mostsevere lesions located in the medial coronoid process of the ulna and medial humeral epicondyle). Synovitis scores were mild overalland correlated only weakly with macroscopic cartilage damage. Intra-articular osteochondral fragments either free or attached tothe synovium were found in 10 joints. Macroscopic or histologic evidence of a fragmented coronoid process was not found even inthose cases with intra-articular osteochondral fragments. Lesions observed in these animals are most consistent with synovial osteo-chondromatosis secondary to degenerative joint disease. The pathogenesis for the medial compartmentalization of these lesionshas not been established, but a fragmented medial coronoid process or osteochondritis dissecans does not appear to play a role.

Keywordsdegenerative joint disease, elbow joint, feline, histopathology, medial compartment joint disease, synovial osteochondromatosis

Appendicular degenerative joint disease (DJD) is a condition

commonly present in domestic cats. Prevalence of radiographic

signs of appendicular DJD in this species varies with age and

has been reported to range from 16.5% to 91%.5,12,15,19,29

Joints reported to be most commonly affected in prospective

studies are hip and stifle19 or shoulder and elbow.29 Radio-

graphic evidence of DJD in the elbow joint in cats has a preva-

lence of approximately 41%, and bilateral disease has been

reported in 28% of cases.19

The predominant cause of DJD in the cat has not been

identified,18 and it is suggested that most cases of feline DJD are

primary or idiopathic.4,5,12 The elbow joint is commonly

affected by DJD in dogs as well,20 but unlike cats, most canine

patients with elbow joint DJD have known underlying predis-

posing factors such as a fragmented medial coronoid process

(FMCP) or osteochondritis dissecans (OCD). To date, these

forms of elbow dysplasia have not been proven to be present

in cats. One report suggested the occurrence of elbow dysplasia

(FMCP) as a cause of elbow disease in a feline patient after

removal of several osteochondral fragments from both elbow

joints.31 As part of a separate study, we have observed similar

fragments in cats with elbow DJD, in which evidence of macro-

scopic cartilage damage is present but with apparently intact

coronoid processes of the ulna on macroscopic examination.11

The presence of free ossified fragments has been identified in

shoulder, stifle, and elbow joints in cats and considered either

osteophytes that have not been completely incorporated within

the epiphysis or ‘‘osteochondromas’’ resulting from hyperplasia

of the synovial membrane and synovial chondrometaplasia.2,32

In neither of these studies was a thorough histopathological

1Comparative Pain Research Laboratory (CPRL), Department of Clinical

Sciences, College of Veterinary Medicine, North Carolina State University,

Raleigh, NC, USA2Population Health and Pathobiology Department, College of Veterinary

Medicine, North Carolina State University, Raleigh, NC, USA3Center for Comparative Medicine and Translational Research, Department of

Clinical Sciences, College of Veterinary Medicine, North Carolina State

University, Raleigh, NC, USA4Department of Clinical Sciences, Surgery Section, College of Veterinary

Medicine, North Carolina State University, Raleigh, NC, USA

Corresponding Author:

D. Lascelles, Comparative Pain Research Laboratory (CPRL), Department of

Clinical Sciences, College of Veterinary Medicine, North Carolina State

University, Raleigh, NC 27606, USA.

Email: [email protected]

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evaluation of the free osteochondral fragments, medial coronoid

process, or synovial membrane reported. Histological changes of

the humeral condyle in cats with and without DJD have recently

been published and suggested concentration of the lesions in the

medial part of the humeral condyle,28 but this work did not eval-

uate other articular surfaces or the synovial membrane, and it was

not designed to look for possible causes of feline elbow DJD.

Even though the prevalence of radiographic signs of DJD in

the elbow joint in cats is high and FMCP has been suggested to

be present in this species, the etiology of feline elbow DJD is

unknown, and the presence of feline elbow dysplasia has not

been confirmed. The objective of this study is to report the his-

tological characteristics of the articular surfaces, synovial

membranes, and intra-articular osteochondral fragments in

elbow joints from cats with and without DJD and compare the

findings with those reported to be present in dogs with FMCP.

We hypothesized that elbow joints with macroscopic evidence

of DJD and the presence of intra-articular osteochondral frag-

ments had histological evidence of a fragmented coronoid pro-

cess (similar to dogs) and that the degree of macroscopic and

histological damage of the articular surfaces correlated with the

severity of synovial inflammation and hyperplasia.

Materials and Methods

This study was a prospective study using autopsy material.

Animals

Thirty adult cats, scheduled for euthanasia at a local animal

shelter, were included. These animals were part of a previous

study performed by the same laboratory.11 Selection of these

animals was such that will increase the likelihood of finding

animals with different degrees of osteoarthritis (eg, selecting

for older animals to increase the chance of finding joints with

DJD). Animals were euthanized with an overdose of barbitu-

rates for reasons unrelated to this study (population control).

Age and sex of the cats were recorded. Clinical history of these

animals prior to euthanasia was not known.

Macroscopic Examination

Immediately after euthanasia, both elbow joints of each cat

were opened and the joints were visually inspected for the pres-

ence of macroscopic lesions as described previously.11 The

articular cartilage of the humerus, radius, and ulna of each joint

was evaluated grossly for fibrillation and/or erosion of the car-

tilage surface using India ink23 as previously reported.11

Briefly, after gross observations were recorded, the cartilage

surfaces were painted with India ink twice, rinsing the cartilage

with water 3 minutes after the ink was applied. The severity of

surface damage of the articular cartilage was scored based on

ink retention and graded according to the scale described in a

previous study:33 grade 1—intact surface: surface appears nor-

mal and does not retain any ink; grade 2—minimal fibrillation:

site appears normal before staining but retains India ink as

elongated specks or light gray patches; grade 3—overt fibrilla-

tion: the cartilage is velvety in appearance and retains ink as

intense black patches; and grade 4—ulceration: loss of carti-

lage exposing the underlying bone. Only severity of cartilage

damage was graded, independently of the extent of the lesion.

Early during the dissection, the medial coronoid process was

also grossly evaluated for the presence of cartilage fissures

or intra-articular fragments that could be secondary to medial

coronoid fragmentation.

Histopathology of Elbow Joints

Following macroscopic examination, a section containing the

articular surfaces of the proximal ulna and radius and distal

humerus, as well as a sample of the joint capsule/synovium,

was immediately placed in 10% neutral buffered formalin for

at least 48 hours. Decalcification of the bone specimens was

achieved using 10% formic acid solution for a variable time

length (7–14 days) depending on the size of the samples. After

decalcification, sections perpendicular to the articular surfaces

of each bone were cut making sure the area with the most

severe macroscopic cartilage fibrillation was included. These

sections were performed so that they included the coronoid and

anconeal processes of the ulna in all cases following a parasa-

gittal plane. Sections of the humerus and radius were per-

formed in the frontal plane. Two serial sections of the bone

specimens were mounted onto glass slides and stained with

hematoxylin and eosin (HE) and Safranin-O (SO). Sections

of joint capsule/synovium were stained with HE. Osteochon-

dral fragments found within the joint or attached to the joint

capsule were collected, processed, and stained in the same

manner as the bone specimens.

The bone, joint capsule, and osteochondral fragments were

evaluated microscopically (Olympus microscope BX41TF

[Olympus America, Center Valley, PA]; Nikon microscope

camera DS 2Mv [Nikon, Tokyo, Japan]). A descriptive approach

was used to evaluate the histological changes present in the

articular cartilage and subchondral bone, using combination of

the Mankin and OARSI (Osteoarthritis Research Society Inter-

national) histological and histochemical scoring systems to cre-

ate a unique scoring system relevant to this study (Suppl. Table

S1).21,26 This enabled semi-quantitative evaluation of structural

changes in all layers of the uncalcified hyaline cartilage, calci-

fied cartilage zone, tidemark integrity, and the intensity of SO

staining as well as changes identified in the subchondral bone.

The sections were evaluated at different magnifications for the

individual parts of the scoring system. The degree of synovitis

was evaluated and graded using the grading system previously

described by Krenn et al17 (Suppl. Table S2). Changes observed

in 3 histologic structures (synovial lining cell layer, stroma cell

density, and inflammatory infiltrate) were assigned a numerical

score: none (0), slight (1), moderate (2), and strong (3). These

individual scores were summed to determine a final total

score, and the final scores for each sample were interpreted

as follows: 0 to 1, no synovitis; 2 to 4, low-grade synovitis;

and 5 to 9, high-grade synovitis. Evaluation was performed

2 Veterinary Pathology




at the area of the specimen with the most marked histo-

pathological alterations.

Statistical Analysis

The mean + standard deviation (SD) macroscopic and mic-

roscopic cartilage damage scores of the ulna, humerus, and

radius were compared using the Wilcoxon signed-rank test.

Bonferroni correction for multiple comparisons was used, and

results were considered significantly different when P < .016.

Spearman’s rank correlation coefficient was used to assess

correlation between synovitis scores of each joint and the

worse macroscopic and microscopic cartilage damage scores

(the highest score of the 3 bones of each joint). Values of

P < .05 were considered significant.

Results

A total of 30 animals were included in the study. There were 19

females and 11 males. Age was known in 18 animals and ran-

ged from 7 to 19 years. Because of unknown previous history,

age was speculated in 12 animals; 9 were considered young

adults (age range approximately between 2 and 7 years), and

in 3, age was suspected to be at least between 10 and 13 years.

Macroscopic Findings

Twenty-two of the 30 cats (73.3% of cats; 39 elbow joints; 115

of 180 bones; 64% of all articular surfaces) had macroscopic

lesions of the articular cartilage that ranged from mild fibrilla-

tion to complete ulceration of the cartilage with exposure of the

subchondral bone. Sixty-five articular surfaces (36%) were

grossly normal, and there was no retention of India ink (grade

1); 78 (43%) had mild macroscopic cartilage fibrillation (grade

2); 19 (11%) had severe macroscopic cartilage fibrillation

(grade 3); and 18 (10%) had complete ulceration of the articular

cartilage with exposure of the subchondral bone (grade 4)

(Table 1; Fig. 1).

Macroscopic cartilage lesions were bilateral when present,

and the degree of damage to the articular surfaces was similar

in both elbow joints. Macroscopic lesions of the articular carti-

lage with the most severe degree of cartilage erosion were

located in the medial compartment of the joints (articular sur-

face of the medial coronoid process and medial aspect of the

humeral condyle). All animals that did not have macroscopic

lesions were young adults (estimated between 2 and 7 years

of age), and the most severe lesions with ulceration of the

cartilage were found only in animals older than 10 years.

Microscopic Findings

The articular surface of 180 bones (radius, ulna, and humerus

of each elbow joint) was evaluated grossly, with 176 bones

evaluated histologically (4 specimens were not processed

appropriately and slides were not considered of sufficient

quality for evaluation). These 176 samples represent 1 section

from each of the 3 bones comprising the elbow joint, taken

bilaterally from 30 cats.

Of the 64 grossly normal articular surfaces that were evalu-

ated histologically, 40 were histologically normal and abnorm-

alities were detected in 24 specimens. Of the 112 grossly

abnormal articular surfaces evaluated histologically, 10 were

histologically normal and 102 were histologically abnormal

(Table 2). Histological abnormalities are described below.

Histological Characteristics of Macroscopically NormalSamples

Sixty-four samples with no India ink retention by the cartilage

were evaluated histologically; of those, 40 samples were also

considered microscopically normal. These samples were char-

acterized by the absence of cartilage fibrillation, normal den-

sity and number of chondrocytes organized in columns,

normal intensity of SO staining, a single tidemark not crossed

by blood vessels, and absence of changes in the subchondral

bone, such as no increase in woven bone or islands of cartilage

or fibrosis in the bone marrow spaces (Suppl. Figure S1).

Microscopic lesions were observed in 24 samples without any

evidence of macroscopic fibrillation of the cartilage (no India

ink retention by the cartilage surface). These lesions were char-

acterized by moderate to severely decreased SO staining,

decreased number and size of chondrocytes, and occasionally

deep fissures separating the hyaline cartilage from the deeper

calcified cartilage (at the level of the tidemark; 4 specimens)

(Fig. 4). No superficial fibrillation of the hyaline cartilage was

present in these cases. These lesions were always observed as

focal, particularly in the ulna, located in the articular cartilage

covering the coronoid process. Fissures or microfractures of the

subchondral bone at this level that could indicate deeper lesions

or diseases involving the subchondral bone were not observed.

Table 1. Details of the Severity Grades of Macroscopic Cartilage Damage of the Humerus, Radius, and Ulna Articular Surfaces.

Macroscopic Grading System—India Ink Retention Score

Grade 1 Grade 2 Grade 3 Grade 4 Score, Mean (SD)

Humerus (n ¼ 60) 21 21 9 9 2.1 (1.05)Radius (n ¼ 60) 25 33 2 0 1.6 (0.5)Ulna (n ¼ 60) 19 24 8 9 2.1 (1.02)Total (N ¼ 180 bones) 65 78 19 18

Grade 1, no lesions; grade 2, mild fibrillation; grade 3, moderate fibrillation; grade 4, cartilage ulceration.

Freire et al 3




Figure 1. Humeral condyles; cat. Macroscopic cartilage fibrillation grades 1 to 4 using the India ink retention grading system. (a) Cartilage fibril-lation grade 1, no ink retention. (b) Cartilage fibrillation grade 2 or mild fibrillation in a specimen in which cartilage fibrillation was difficult toappreciate before ink application. (c) Cartilage fibrillation grade 3 or moderate fibrillation. In this joint, degenerative joint disease was grosslyevident before ink application. (d) Cartilage fibrillation grade 4 or cartilage ulceration with exposure of the subchondral bone, which does notretain ink. Figure 2. Elbow joint; cat No. 24. Intra-articular osteochondral fragment. A free intra-articular osteochondral fragment is present inthe cranial aspect of the elbow joint. The fragment is next to the medial coronoid process of the ulna and medial epicondyle of the humerus.Figure 3. Intra-articular osteochondral fragments; cat No. 24. Three intra-articular osteochondral fragments found in the same elbow displayedin Fig. 2. The 2 larger fragments were in the cranial aspect of the joint, one free and the other attached to the joint capsule. Size of intra-articularfragments ranged from 3 to 6 mm. This animal had intra-articular osteochondral fragments in both elbows.





Adjacent to the focal lesions, which were approximately 400 to

500 mm in length, the articular cartilage was normal.

Histological Characteristics of Macroscopically AbnormalSamples

Macroscopic fibrillation of the articular surfaces was accompa-

nied by microscopic lesions in 102 of the 112 macroscopically

abnormal samples evaluated. Ten specimens with macroscopic

fibrillation of the cartilage were considered normal histologi-

cally. Histological lesions were characterized by different

degrees of fibrillation of the hyaline cartilage, decreased inten-

sity of SO staining, decreased number and size of chondrocytes

as well as disorganization of the chondrocyte columns, and

changes in the subchondral bone.

In cases with mild or moderate degrees of macroscopic car-

tilage damage (India ink retention grades 2 and 3), the histolo-

gical lesions were also relatively mild or moderate and

consisted of cartilage surface discontinuity with vertical fis-

sures extending into the superficial, mid, or deep zones; occa-

sionally, fissures extending into the calcified cartilage zone or

the subchondral bone were also observed. Cell death was iden-

tified adjacent to the fissures, but chondrocyte proliferation

was not appreciated in those areas. SO staining in areas of car-

tilage fibrillation was of variably decreased intensity, from

slightly decreased to no staining at all (Figs. 5, 6). Lesions

observed in the subchondral bone immediately below the

articular cartilage were classified as mild and were character-

ized by fibrosis in the bone marrow spaces with occasional foci

of cartilage islands. The amount and distribution of woven

bone in the subchondral bone was considered abnormal in 3

cases with macroscopic cartilage damage classified as grade 3.

Cases with the most severe degree of macroscopic cartilage

damage (India ink retention grade 4) showed complete ulcera-

tion, with hyaline cartilage matrix loss exposing the calcified

cartilage zone or the subchondral bone to the intra-articular

space (Fig. 7). Cell death was identified adjacent to the fissures

and hypertrophic chondrocytes were occasionally seen adja-

cent to areas of severe cartilage fibrillation, but chondrocyte

proliferation was not identified in those areas (Fig. 8). SO stain-

ing adjacent to the areas of severe cartilage fibrillation was

severely decreased in intensity or absent in all cases. Changes

in the subchondral bone (fibrosis/cartilage islands and/or

woven bone) were present in all cases with grade 4 macro-

scopic cartilage fibrillation. Fibrosis and cartilage islands in the

subchondral bone ranged from mild to severe. These areas

appeared as discrete foci of hypertrophic chondrocytes

embedded in the chondroid matrix (‘‘cartilage islands’’) and/

or fibrovascular granulation tissue filling bone marrow spaces

in close proximity to the exposed subchondral bone surface

(Fig. 9). Replacement of mature lamellar bone by woven bone

was detected by polarizing light in 8 of 18 cases with severe

macroscopic cartilage damage, and in these cases, the articular

surface was completely ulcerated and the subchondral bone

exposed. Woven bone was always surrounding the areas of car-

tilage islands and bone marrow spaces that were filled with

fibrosis.

Changes in the density of the subchondral bone were not

appreciated. The tidemark was intact, single, and not crossed

by blood vessels in any case, including those with severe

damage of the articular cartilage.

Medial Coronoid Process

Visual inspection of the medial coronoid process did not reveal

the presence of fissures in the cartilage, in situ fractured coro-

noid fragments, or free fractured fragments within the joint. In

those joints in which intra-articular osteochondral fragments

were present, the coronoid process was macroscopically intact.

Microscopically, fissuring of the subchondral bone of the med-

ial coronoid process was not identified in any cases, neither in

cases with intact overlying articular cartilage nor in cases with

severe cartilage damage. Subjective evaluation of cartilage

thickness, osteocyte density of the subchondral bone, and bone

porosity in the subchondral bone of the coronoid process was

normal.

Relationship of Macroscopic and Microscopic LesionsBetween Different Bones Within a Joint

Macroscopic cartilage damage scores (mean + SD) using the

India ink grading system were significantly higher for the ulna

(2.1 + 1.02; P ¼ .0001) and the humerus (2.1 + 1.05; P <

.0002) compared with the radius (1.6 + 0.5). No differences

were found when the ulna and humerus were compared (P ¼.7) (Table 1). Macroscopic cartilage lesions were bilateral, and

the degree of damage of the articular surfaces was similar in both

elbow joints. The location of the lesions with the most severe

cartilage fibrillation indicated the presence of disease in the

medial compartment of the elbow joint with the articular surface

of the medial coronoid process and the medial epicondyle of the

humerus having the most severe degree of cartilage fibrillation.

Microscopic cartilage damage scores (mean + SD) were

significantly higher for the ulna (5.54 + 4.3) compared with

the radius (2.5 + 2.6; P < .0001) and the humerus (3.8 +3.9; P < .0001). Microscopic cartilage damage scores were also

significantly higher for the humerus compared with the radius

(P ¼ .007).

Table 2. Distribution of Macroscopic and Histological Normal andAbnormal Articular Surfaces by Bones.

Histologically

Macroscopically Normal Abnormal

Normal (n ¼ 64) Humerus 15 5Radius 17 8Ulna 8 11

Abnormal (n ¼ 112) Humerus 6 33Radius 4 31Ulna 0 38

Total (N ¼ 176) 50 126

Freire et al 5




Figure 4. Ulna; cat No. 21. Early histological lesions in articular cartilage. (a) Superficial cartilage fibrillation is not present. A focal area of dis-organization and decreased number of chondrocytes is present (arrow). A fissure is separating the hyaline cartilage from the calcified cartilagezone, at the level of the tidemark (arrowhead). Macroscopic appearance of this articular cartilage was normal. Hematoxylin and eosin (HE). (b)The affected area has loss of Safranin-O (SO) staining (arrow). Figure 5. Humerus; cat No. 18. Mild cartilage fibrillation. Superficial fibrillation ofthe articular cartilage with fissures that extend into the superficial/mid-zone of the hyaline cartilage (asterisks). Mild disorganization anddecreased number of chondrocytes in the affected area are present. Area of cartilage and subchondral bone with increased stain intensity isa folding artifact. HE. Figure 6. Ulna; cat No. 23. Moderate cartilage fibrillation. Multiple vertical fissures extend into the deep zone of the hya-line cartilage (arrow), the number of chondrocytes is decreased, and cell death would be appreciated at higher magnification adjacent to thefissures. Black staining in the fissures is India ink retention. Cell proliferation is not present. HE. Figure 7. Ulna; cat No. 24. Severe cartilagefibrillation with ulceration. Cartilage fibrillation with ulceration and exposure of the calcified cartilage zone is present. In the hyaline cartilageadjacent to the ulcerated region, decreased size and number of chondrocytes is evident. HE. Figure 8. Ulna; cat No. 22. Occasionally, hyper-trophic chondrocytes were appreciated adjacent to areas of severe cartilage fibrillation. Cell proliferation with clusters of normal-sized chon-drocytes was not seen in any case. SO.





Intra-articular Osteochondral Fragments

A total of 16 intra-articular osteochondral fragments were eval-

uated grossly and histologically. Those fragments were found

in 10 joints (affecting 6 different animals). The articular carti-

lage was ulcerated in at least one of the bones in all of those

joints except in 2, in which the macroscopic cartilage damage

was scored as 2 (mild cartilage fibrillation). Six joints had sin-

gle fragments and 4 joints had multiple fragments. These frag-

ments were either attached to the synovial membrane or free as

intra-articular bodies. Macroscopically, the osteochondral

Figure 9. Ulna; cat No. 24. Cartilage ulceration and subchondral bone lesions. (a) Articular surface of the ulna is ulcerated with exposure anderosion of the subchondral bone. The subchondral bone underneath the ulcerated articular surface has fibrosis in the bone marrow spaces andcartilage islands. New woven bone was located surrounding the cartilage islands and bone marrow spaces filled with fibrosis. Hematoxylinand eosin (HE). (b) Higher magnification view of the subchondral bone with cartilage islands (asterisks) and fibrovascular granulation tissue fillingthe bone marrow spaces (arrowheads). HE. (c) Foci of cartilage in the subchondral bone are highlighted by uptake of Safranin-O (SO) stain.Figure 10. Intra-articular osteochondral fragment; cat No. 15. Image shows an intra-articular osteochondral fragment composed exclusivelyof cancellous bone with well-organized trabeculae and marrow spaces. HE. Figure 11. Intra-articular chondral fragment; cat No. 24. Someintra-articular fragments were composed exclusively of fibrocartilage, chondroid matrix, and chondrocytes as the one shown in the image. Theywere surrounded by a thin layer of dense fibrous tissue similar to the fragment shown in Fig. 10. HE. Figure 12. Intra-articular osteochondralfragment; cat No. 15. In most cases, osteochondral fragments were composed of a mixture of trabecular bone with marrow spaces, hyalinecartilage, and areas of fibrous tissue. HE. Figure 13. Intra-articular osteochondral fragment; cat No. 28. Two trabeculae of viable bone resideon each side of hematopoietic cells. HE. Figure 14. Synovial membrane; cat No. 24. Chondroid metaplasia. Chondroid metaplasia of the syno-vial stroma was characterized by foci of cartilage (asterisk) in various stages of differentiation that progressed into endochondral ossification.Areas of metaplasia were not associated with inflammatory infiltrates (score 1—few, mostly perivascular infiltrates). Synovial hyperplasia is not aprominent feature of this disease. Synovial lining (þ) in this case showed only mild synovial hyperplasia (score 1—lining cells form 2–3 layers).HE. Figure 15. Synovial membrane; cat No. 6. Lymphoplasmacytic infiltrates. Synovial lymphoplasmacytic infiltrates, score 1 (as observed inmost cases). The lymphoplasmacytic infiltrates are located perivascularly in the synovial stroma, with little to no hyperplasia of the overlyingsynovium (asterisk). This degree of inflammation in some cases corresponded with severe cartilage fibrillation and ulceration. HE.

Freire et al 7




fragments where white to pink, flat oval to round, and ran-

ged from 3 to 6 mm (maximum length) (Figs. 2, 3). Micro-

scopically, these fragments contained different amounts of

well-organized cancellous bone with marrow spaces that

occasionally contained hematopoietic cells. Some fragments

also contained hyaline cartilage and fibrocartilage. Different

stages of endochondral ossification were present in those

areas of mixed tissue types. The outermost layer was com-

monly a thin layer of dense fibrous tissue. More commonly,

a mixture of different tissue types was found, but occasion-

ally fragments were exclusively of either fibrocartilage or

organized trabecular bone (Figs. 10–13).

Synovial Membrane Findings

A total of 56 synovial membrane tissue samples were evaluated

histologically (from 56 different elbow joints). Four samples

from elbow joints of 4 different animals were not considered

of appropriate quantity or quality for histological evaluation

and were not graded. Overall, there was only mild inflamma-

tion in the synovium, very little synovial hyperplasia, and only

weak correlation of synovial lesions with severity of macro-

scopic and microscopic cartilage lesions. Final synovitis scores

of all samples evaluated ranged from 0 to 5 (maximum possible

score ¼ 9).

Synovial membrane samples considered normal (final score

0–1; n ¼ 32) were characterized by normal synovial lining cell

layer thickness, normal cellularity of the synovial stroma, and

no inflammatory infiltrate present (Suppl. Table S2). The

macroscopic cartilage damage score (the highest score of the

3 bones) of those joints with normal synovial membrane sam-

ples ranged from 1 to 4 (normal to severe cartilage fibrillation).

Synovial membrane samples with the highest synovitis scores

(4–5; n ¼ 9) were characterized by moderate enlargement of

the synovial lining layer (score 2), mild increase in density of

resident cells (score 1), and mild inflammatory infiltrate (score

1). Inflammatory infiltrates consisted of lymphoplasmacytic

micronodules located perivascularly in the synovial stroma

(Fig. 15). The macroscopic cartilage damage score (the highest

score of the 3 bones) of those joints with the highest micro-

scopic scores for the synovial membrane samples ranged from

2 to 4 (mild to severe cartilage fibrillation).

The synovial lining was never ulcerated, and multinucleated

cells were never seen in the synovial lining cell layer or in the

synovial stroma, even in cases in which the subchondral bone

was denuded of articular cartilage. None of the samples had

inflammatory infiltrates graded as severe (score 3), and only

2 synovial membrane samples (joints from the same animal)

had an inflammatory infiltrate graded as moderate (score 2).

Microscopic changes different from those evaluated for the

synovitis severity score were observed. Chondroid metaplasia

of the synovial stroma was identified in 2 cases. These areas

appeared as micronodules of metaplasia of the hyperplastic

synovium into cartilage, of varying stages of differentiation

that seemed to undergo endochondral ossification to form bony

nodules in some cases. These areas of metaplasia were not

associated with inflammatory infiltrates (Fig. 14).

Synovitis severity scores were significantly but weakly and

moderately correlated with the highest macroscopic (r2 ¼0.3768; P ¼ .0042) and microscopic (r2 ¼ 0.4226; P ¼ .0012)

cartilage damage scores of the joints, respectively.

Discussion

Results of this study are the first description of the histopatho-

logical characteristics of feline elbow joints with and without

macroscopic DJD lesions. Lesions were present bilaterally, and

the ulna was the bone with the most severe degree of cartilage

damage in both macroscopic and microscopic cartilage damage

scoring systems. Cartilage lesions ranged from superficial

fibrillation of the cartilage to complete ulceration with expo-

sure of the subchondral bone. The most severe macroscopic

as well as histological lesions of the articular surfaces were

identified within the medial compartment of the elbow joint,

specifically in the medial coronoid process of the ulna and the

medial epicondyle of the humerus. Medial compartmentaliza-

tion of the lesions in feline elbow joints has been documented

macroscopically elsewhere,2 and concentration of microscopic

lesions in the medial part of the humeral condyle also has been

documented.28 Medial compartment elbow disease is well

recognized in dogs as a result of elbow dysplasia (FMCP and

OCD of the medial humeral epicondyle).3,9,24 However, our

observations did not reveal any of the features that are reported

in dogs with a fragmented coronoid process (microcracks in the

subchondral bone, increased porosity, and loss of osteo-

cytes).6,13 Histomorphometry was not performed in our study,

but increased porosity and decreased osteocytes were seen only

in the areas of microcracks of the subchondral bone in dogs,

and microcracks were not present in our specimens. It is possi-

ble that fissures may have been missed during processing of the

samples for histopathological evaluation. Nevertheless, since

no evidence of FMCP or a histologic reaction to an adjacent

microfracture was present in any of the specimens and fissuring

or fracture of the coronoid process was not seen during macro-

scopic evaluation of any joints, we conclude that fragmentation

of the coronoid process is not part of the pathogenesis of feline

elbow DJD in the cases described in this study. Some of the

changes observed in the subchondral bone in the samples eval-

uated in this study are similar to those described in the sub-

chondral bone of the medial coronoid process from dogs with

FMCP disease (cartilage islands and fibrosis of the bone mar-

row spaces).13 These lesions are nonspecific responses of bone

to a variety of insults and are not unique to FMCP. Unlike

lesions in the canine coronoid processes, subchondral bone

changes in the feline samples evaluated here were present only

when cartilage erosion was so severe that the hyaline cartilage

was ulcerated. In the canine study by Goldhammer et al,13 hya-

line cartilage was still present on the articular surface of the

medial coronoid process in cases with cartilage islands in the

subchondral bone. The cartilage islands within the subchondral

bone lesions were likely secondary reactions to the disease that





leads to medial coronoid fragmentation, unlike in our samples

in which subchondral bone findings were likely consequence of

the degree of cartilage degradation rather than pathology origi-

nating in the subchondral bone.

The cause of elbow DJD in cats with this pattern of medial

compartmentalization is unknown. One of the theories pro-

posed for the pathogenesis of FMCP in dogs is the presence

of abnormal loading forces in the elbow joint resulting from

asymmetric growth of the radius and the ulna, which causes

increased loads in the coronoid process and subsequent frag-

mentation. Perhaps the same theory could explain why the

lesions are concentrated in the medial compartment of the

elbow joints in cats. However, further investigation will be nec-

essary to elucidate why fragmentation of the medial coronoid

process does not happen as a result of these theoretical abnor-

mal loadings in feline species. One possibility is that cats do not

have underlying lesions of OCD in their coronoid processes,

since we did not see evidence of osteochondritis or OCD in any

of the samples examined. A less likely possibility is that ero-

sion of the cartilage of the medial coronoid process and medial

humeral epicondyle is due to contact with the intra-articular

osteochondral fragments, which were commonly located cra-

niomedial in the elbow joint in close proximity to the coronoid

process. However, this pattern of medial compartmentalization

of the cartilage damage was also observed in joints without

intra-articular osteochondral fragments, so this does not fully

explain the pattern of cartilage damage observed herein.

Histopathological characteristics of the free intra-articular

osteochondral fragments and changes observed in the synovial

stroma (chondroid metaplasia and endochondral ossification)

seem to indicate that those fragments originate from the synovial

membrane and therefore are consistent with synovial osteochon-

dromatosis secondary to DJD. Unlike primary synovial osteo-

chondromatosis, in the secondary form, the intra-articular

nodules are less numerous and often mixed with other forms

of synovial proliferation and metaplasia, as well as with erosive

changes in the articular cartilage that are more marked than is the

degree of synovial proliferation,22,25 which is consistent with our

findings. A few cases of synovial chondromatosis in canine spe-

cies are described in the literature, affecting shoulder, stifle,

elbow, and tarsal joints.1,7,8,10,14,30 Mention of feline synovial

chondromatosis in the literature is scarce. In older publications,

diagnosis was made based on radiographic findings without

gross or histopathological confirmation.16 In more recent

reports, intra-articular mineralizations found in shoulder and

elbow joints are referred to as ‘‘osteochondromas,’’ but macro-

scopic and histopathological characteristics are consistent with

synovial osteochondromatosis as described in this study.2 These

intra-articular fragments may not be visible radiographically

depending on their degree of calcification, and so it is possible

that synovial osteochondromatosis with articular cartilage

erosion may be present in some joints without radiographic

evidence of DJD as has been published previously.11

Severe synovial inflammation was not seen in any of the

samples evaluated, and overall there was only mild inflamma-

tion in the synovium and very little synovial lining hyperplasia

even in those elbow joints in which the articular cartilage was

ulcerated. This suggests that the elbow lesions in our cases were

not primarily inflammatory in origin. The joints with the most

severe cartilage fibrillation tended to have the highest synovitis

scores, but correlations of the degree of synovitis with macro-

scopic and microscopic cartilage damage scores were only weak

and moderate, respectively. Goldhammer et al13 reported the

degree of synovitis in dogs with different degrees of cartilage

fibrillation secondary to FMCP, and similar to our study, the

synovitis scores were low, even in cases with ulceration of the

articular cartilage. These results are consistent with synovitis

scores reported by Krenn et al,17 in which the mean synovitis

score of patients diagnosed with osteoarthritis was only 2 (range,

0–6). It is not surprising, then, that ulceration of the epithelial

lining of the synovial membrane or severe inflammatory infil-

trate of the synovial stroma was not seen in our samples since

these features seem to correspond only with reactive or rheuma-

toid arthritis. The degree of synovitis present in dogs with syno-

vial osteochondromatosis has not been reported, but clinically

these animals have pain on manipulation of the joints. If the

degree of synovitis is mild, as we found in the feline samples,

the source of pain in these patients may be coming from a source

other than the inflamed synovial membrane.

Twenty-four samples considered normal macroscopically

were found to be abnormal on histopathologic evaluation. The

lesions observed histologically could be considered early

changes in the process of cartilage degradation, before any

abnormalities are detected on the cartilage surface. Initially,

clefts deep in the hyaline cartilage without any superficial

fibrillation were suspected to be processing artifacts, as has

been suggested in other studies.13 However, a decrease in the

number of chondrocytes and a decrease in SO staining in those

areas were also seen, and so the changes were considered real.

These results are in agreement with a recent publication in

which diffusion parameters (diffusion-weighted spin-echo

magnetic resonance imaging sequences) were used to assess

disease progression of the articular cartilage, and results sug-

gested that collagen architecture in the deep cartilage is altered

early in the process of cartilage damage.27 These recent find-

ings conflict with the current histopathological grading sys-

tems, which are based on the assumption that cartilage

damage is initiated at the cartilage surface and propagates

deeper into cartilage as osteoarthritis progresses. On the other

hand, 10 samples evaluated were graded normal histologically

but abnormal macroscopically (Indian ink was retained by the

articular surface). In these cases, the area and the degree of ink

retention was minimal, and it may represent only mechanical

disruption of the articular surface rather than the result of

altered collagen architecture and cartilage degradation. In addi-

tion, the areas of cartilage fibrillation were so small that it is

possible that they were missed during processing.

In addition to subjective comparisons between the lesions

present in elbow joints of our cats with lesions reported in other

species, we used established scoring systems to grade the

changes present in our samples of cartilage, bone, and syno-

vium. After evaluation of articular surfaces that had lesions

Freire et al 9




of varying severities, it was noted that some of the features used

to differentiate severity grades in established grading systems

were not present in our samples. The grading system by Man-

kin et al21 considers features such as chondrocyte cloning, pres-

ence of pannus, or blood vessels crossing the tidemark as

indicators of cartilage degradation, and these were not identi-

fied in the specimens we evaluated; also, the Mankin system

does not evaluate subchondral bone changes. In the same way,

the OARSI system26 establishes grades of cartilage degradation

using some features that could not be observed in the samples

we evaluated (eg, cartilage edema, chondrocyte clustering),

and even though this system included evaluation of changes

in the subchondral bone, the changes to be evaluated also dif-

fered from our observations. For these reasons and since these

systems have not been validated in feline species, we devel-

oped a scoring system relevant for this study that considered

features observed in the specimens evaluated. The modification

of the scoring system proposed here may be a useful reference

for the evaluation of cartilage damage in other animal species

for which the previously reported systems are not fully applica-

ble as in feline joints.

On the basis of our results, we reject the hypothesis that

elbow joints with macroscopic evidence of DJD and the pres-

ence of intra-articular osteochondral fragments have histologi-

cal evidence of a fragmented coronoid process. The degree of

synovitis was correlated with the degree of cartilage damage,

but this correlation was weak or moderate, and overall the

degree of inflammation of the synovium was mild, even in

cases with hyaline cartilage ulceration. The presence of intra-

articular osteochondral fragments in the elbow joint in cats is

consistent with synovial osteochondromatosis secondary to

DJD. Articular cartilage erosion is more severe in the medial

compartment of the joint (medial coronoid process of the ulna

and medial epicondyle of the humerus), for which no explana-

tion has been identified. The lack of synovial inflammation

even in cases with severe cartilage erosion could explain the

previously reported absence of pain on manipulation of joints

with radiographic signs of DJD in some cats. In addition, the

presence of pain on manipulation of joints with DJD may not

be explained by synovitis.

To our knowledge, this is the first report of macroscopic and

histologic lesions of the elbow joint in cats, and even though

our study was not designed to look at the prevalence of elbow

DJD, we know from previous studies that feline elbow DJD is a

condition that can be seen radiographically in 41% of cases.

We believe this is an underestimation of the prevalence of this

disease since most lesions of the cartilage seen grossly and his-

tologically are grades 1 and 2 (mild/moderate), which will not

be seen radiographically unless other degenerative changes are

present in the joint, such as osteophytes. The most severe

macroscopic as well as histological lesions of the articular

surfaces were identified within the medial compartment of

the elbow joint, and they occur without evidence of primary

inflammatory disease, OCD, or FMCP. Cartilage damage

ranged from superficial fibrillation to complete ulceration, and

in the most severe cases, subchondral bone lesions such as

cartilage islands and fibrovascular granulation tissue filling

bone marrow spaces were identified. The degree of inflamma-

tion of the synovium was mild, even in cases with hyaline car-

tilage ulceration, and correlation with the degree of cartilage

erosion was weak to moderate. Intra-articular osteochondral

fragments found within the elbow joint were most consistent

with synovial osteochondromatosis secondary to DJD. This is

a common degenerative disease of the elbow joint in cats that

has been overlooked, and the etiology is unknown.

Acknowledgements

We gratefully acknowledge the competent assistance of Mrs Monica

Mattmuller of the Histology Laboratory of the Veterinary College

of North Carolina State University for the preparation of the histolo-

gical sections and special stains.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to

the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the

research, authorship, and/or publication of this article: This study was

supported by the Comparative Pain Research Laboratory at North Car-

olina State University and a grant from Novartis Animal Health (Global

Fellowship Program). Mila Freire was receiving salary support from

Morris Animal Foundation during the preparation of this manuscript.

Supplemental Material

The online supplemental tables and figures are available at http://

vet.sagepub.com/supplemental

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Freire et al 11




92

SUPPLEMENTAL MATERIAL

Figure S1: Ulna; cat. Normal articular cartilage. Hyaline articular cartilage is divided into

superficial, mid and deep zones and it is separated from the calcified cartilage zone by the

tidemark. HC= Hyaline cartilage; CCZ= Calcified cartilage zone; SB= subchondral bone.

Hematoxylin-Eosin (HE) on the left, Safranin-O (SO) on the right.

93

Table S1 – Microscopic Cartilage Damage grading system – Modification of the OARSI and

Mankin histological and histochemical scoring Systems.

1. Structure Cartilage Score

Normal

Superficial irregularities

Clefts to mid zone

Clefts to deep zone

Clefts to tidemark

Exposure of subchondral bone

0

1

2

3

4

5

2. Tidemark

Normal

Crossed by blood vessels or double tidemark

0

1

3. Chondrocytes

Normal density and organization

Decreased density and disorganized

0

1

4. Safranin-O staining

Normal

Slight reduction superficially

Moderate reduction

Severe reduction

No stain

0

1

2

3

4

5. Cartilage islands in subchondral bone

Absent

Mild

Moderate

Severe

0

1

2

3

6. Woven bone

Normal

Increased and/or abnormal distribution mild

Increased and/or abnormal distribution moderate

Increased and/or abnormal distribution severe

0

1

2

3

94

Table S2. Histopathological assessment of the three features of chronic synovitis (Krenn et al.

2006).

A. Enlargement of the synovial lining cell layer

0 points The lining cells form one layer

1 point The lining cells form 2-3 layers

2 points The lining cells form 4-5 layes,

few multinucleated cells might occur

3 points The lining cells form more than 5 layers, the lining might be ulcerated and

multinucleated cells might occur

B. Density of resident cells

0 points The synovial stroma shows normal cellularity

1 point The cellularity is slightly increased

2 points The cellularity is moderately increased, multinucleated cells might occur

3 points The cellularity is greatly increased, multinucleated giant cells, pannus formation

and rheumatoid granulomas might occur

C. Inflammatory infiltrate

0 points No inflammatory infiltrate

1 point Few mostly perivascular situated lymphocytes or plasma cells

2 points Numerous lymphocytes or plasma cells, sometimes forming follicle-like aggregates

3 points Dense band-like inflammatory infiltrate or numerous large follicle-like aggregates

D. Final score interpretation

Sum 0 or 1 No synovitis

Sum 2-4 Low-grade synovitis

Sum 5-9 High grade synovitis

95

DISCUSSION

97

The studies described here have been able to confirm that the prevalence of DJD is high

in domestic cats as it had been previously published.1, 2, 5-8

It is possible that the population we

used in the cross-sectional study for determination of the prevalence of radiographic signs of

DJD, have introduced some bias because these animals were selected from a single feline-only

veterinary practice and bias such as life-style, feeding and veterinary care may have been

introduced in these cats, compared to the broader cat population as a whole. Soon after our

work14

was published, another cross-sectional study by Slingerland et al.33

described the

prevalence and clinical features of a population of 100 cats. Although these two works were

designed differently, since the work by Slingerland evaluated only animals older than 6 years of

age, they also found a high prevalence of radiographic signs of DJD (61% of animals had DJD in

at least one joint) and a strong correlation of the presence of DJD with age. One of the questions

that remained open after we determined the high prevalence of this disease was the clinical

significance of this condition in cats. Slingerland et al.33

studied the clinical signs shown by

animals affected with this condition and suggested that lameness does not seem to be a clinical

sign in a large population of cats. Instead, behavioral changes are the most common sign of pain

in cats.

We spent considerable time precisely defining what features were to be classified as

indicative of DJD in the appendicular joints in cats for grading of the radiographs evaluated in

our studies. At the time of publication of the study of prevalence of the radiographic signs of

DJD in feline species, very little information on the association between radiographic signs and

gross or histological features of DJD in feline joints was available, so information used was

mostly changes that are identified in joint degeneration of other species. However, we found that

several radiographic features not normally observed in canine patients (such as medial meniscal

98

mineralization and periarticular mineralizations) were seen commonly in these cats. It could be

argued that the inclusion of such features as indicative of DJD is erroneous because it was not

proven to be secondary to joint degeneration or part of the degenerative process (for example,

dorsal new bone on the intertarsal and tarsometatarsal joints), and other studies have suggested

that periarticular soft tissue mineralizations may not represent DJD.8 However we decided to

include them on the basis of other work we have performed that demonstrated an association

between those features and DJD as measured by cartilage damage.34, 35

For example, our study of

meniscal mineralization in domestic cats we observed that joints with meniscal mineralization

and no other features of DJD, predictably had cartilage erosion and so the decision made was to

include that radiographic finding as a sign of DJD in the stifle joint. Other poorly defined

radiographic features, such as joint-associated mineralizations, may also be associated with joint

degeneration. With respect to the axial skeleton, although it appears that investigators are

describing the same general findings for axial skeleton DJD, the nomenclature used varies, as do

the features included as being indicative of axial DJD.5, 7-9, 36

This problem has recently been

discussed,37

and it is apparent that evaluation of the association between the radiographic

findings in the axial skeleton and their association with macroscopic findings, as we did for the

appendicular joints, needs to be performed for a better understanding of what the radiographic

features commonly found in the axial skeleton corresponds to macroscopically. This will likely

allow for revision and unification of the nomenclature used for describing those lesions.

The very high prevalence of appendicular skeleton DJD and the association between

appendicular and axial skeleton DJD and age that we described is supported by previous and

recent reports.5, 8, 9, 12, 33, 38

Overall despite the high prevalence of radiographic DJD, the severity

scores were relatively low and although this may reflect the particular population studied, it

99

might be that the radiographic severity of DJD in cats is less than in dogs as it has been

suggested in previous studies.8, 9

This needs further investigation.

Because of the different radiographic appearance of DJD in cats compared with dogs, we

evaluated which radiographic findings were most commonly present in the different

appendicular joints in cats and found that the most common radiographic features of DJD were

joint-associated mineralizations for the elbow joint, tarsometatarsal dorsal bone proliferation,

intraarticular mineralizations in the stifle joint and osteophytes in the coxofemoral joint. Except

for the coxofemoral joint, osteophytes were not the most common radiographic sign of DJD, and

this an important feature to emphasize because although the radiographic findings vary according

to the stage of the disease, it is generally accepted that periarticular osteophyte formation of

different degrees of severity are present in any joint affected with DJD. Since other forms of new

bone formation and joint-associated and intra-articular mineralizations were seen commonly in

feline joint with DJD, the sentiment that cats form less new bone in association with DJD than

other species should be clarified. Based on our results, cats form periarticular new bone, but the

radiographic appearance is different to dogs. The fact that some radiographic features not

commonly seen in dogs, such as joint-associated mineralizations and meniscal mineralizations,

were seen commonly in cats, suggests that the radiographic signs of DJD are different in cats

than dogs. This needs further clarification.

The presence of cartilage damage in joints without any radiographic changes indicative of

the presence of DJD is not surprising since it is well known that imaging of cartilage using

radiography is impossible. Cartilage damage is an early change in the process of joint

degeneration and other changes, such as osteophytosis and subchondral sclerosis, become

apparent radiographically only in more advanced stages of the disease. However, based on what

100

we observed, severe cartilage damage with exposure of subchondral bone may be present with

only mild radiographic evidence of DJD, and the prevalence of cartilage lesions in

radiographically normal joints was high in some of the joints evaluated in our study. Clinically

this might result in considering joints as normal when in reality their cartilage is damaged, or

considering that the degree of degenerative disease is mild when severe cartilage damage is

already present. Implementation of joint evaluation by imaging systems that better determine the

state of articular cartilage would allow identification of joint degeneration more accurately and in

early stages. Different degrees of cartilage damage can be detected using diffraction enhanced

radiographic imaging,39, 40

but this imaging modality is not readily available for veterinary

practitioners, even in referral centers. Since conventional radiographs are the easiest indirect and

most used method to evaluate degenerative changes in joints, we evaluated the usefulness of the

radiographic features of osteoarthritis as predictors of articular cartilage degeneration, the same

way that has been described in humans that marginal osteophytes are the most sensitive

radiographic features for detection of osteoarthritis of the tibiofemoral joint.41

Our results

indicate that when considering all the joints, there is statistically significant correlation between

cartilage damage and the detection of osteophytes and joint associated mineralizations, however

this correlation was only fair. When looking at various joints individually, although most

correlations were statistically significant, only the presence of osteophytes and the subjective

radiographic DJD score had a moderate degree of correlation with the presence of cartilage

damage for the elbow and coxofemoral joints. The other correlations evaluated were either only

fair, or not significant as a result of the high number of joints with no radiographic signs of DJD

but with cartilage lesions present. It can be deduced that radiographic signs of DJD in feline

appendicular joints are not sensitive features for detection of DJD.

101

Trying to explain the etiological aspects of the presence of DJD in different appendicular

joints and because of the high prevalence of radiographic evidence of meniscal mineralization

we decided to investigate the pathological aspects associated with the presence of these

mineralizations in the stifle joints in cats. Meniscal mineralization is a poorly understood

condition that has been reported in many species including large non-domestic cats such as

African lions, Bengal and Bengal-cross tigers.16-19, 42

The cause of these mineralizations is

unknown although one theory (phylogenetic theory) suggests that they represent a congenital

vestigial structure that should be interpreted as a variant of normal anatomy.21, 22

In our study

meniscal mineralization was not only correlated with the degree of cartilage damage present in

the joint, but in the case with the largest meniscal mineralization the cartilage lesion of the

medial femoral condyle had form a distinct groove that appeared to articulate with the

mineralization. A previous study also reported the presence of a groove in the medial femoral

condyle that articulated with an ossicle of the medial meniscus in the stifle joint of a tiger

(Pantera tigris)17

, and the authors suggested that the ossicles within the medial meniscus were a

normal adaptive anatomic feature that helped distribution of load through the meniscus thereby

reducing the wear and fatigue of the articular surfaces of the femur and tibia. In contrast to this,

and based on our findings and the degree of damage present in the joints with meniscal

mineralization, we consider the changes in the medial femoral condyle to be degenerative, likely

in response, at least in part, to the presence of the meniscal mineralization.

Although we were able to show a clear relationship between meniscal mineralization and

the presence of cartilage damage and the medial femoral condyle and medial tibial plateau, we

still do not know if the meniscal mineralization is a cause or a result of the cartilage damage. The

fact that there was more cartilage damage on the medial tibial plateau compared with the lateral

102

tibial plateau in the normal stifle might suggest that meniscal mineralization is a response to

degenerative changes in this joint. Our results also suggest that meniscal mineralization may be

associated with medial compartment joint disease of the stifle joint in cats, since cartilage lesions

concentrated in the medial femoral condyle and medial aspect of the tibial plateau. In people,

medial compartment DJD of the knee has been associated with high adduction moment at the

knee during ambulation.43-47

It may be that gait patterns, alteration of gait patterns, or pelvic limb

conformation in some cats may predispose to meniscal mineralization, and this may in turn

hasten the progression of DJD. This of course is speculative, but further investigation of the

condition in cats may help in preventing the disease in this species.

The cause of meniscal mineralization is still debated. Our histologic findings seem to

suggest that menisci undergo a process of ossification, starting with a chondro-osseus

transformation of the fibrocartilage with mineral deposition, ultimately organizing into

cancellous bone and bone marrow structure. That the ossified areas continue to grow by

conversion of fibrocartilage to bone is suggested by the presence of chondro-osseus metaplasia

of the fibrocartilage observed in the periphery of the ossified area. The bilateral symmetrical

appearance of the meniscal mineralizations could support a nondegenerative origin, however,

repetitive microtrauma because of bilateral gait abnormalities, or pelvic limb conformation in

some cats could trigger the degenerative transformation at specific areas of the menisci

bilaterally. In people, chondrocalcinosis of the meniscus has been associated with several distinct

metabolic disorders including hemochroatosis, hyperparathyroidism and hypothyroidism.48

The

association between metabolic disorders and mineralization of menisci in cats is unknown.

103

Another joint in which we focused out attention is the elbow joint which has consistently

been reported as the joint with the more severe radiographic signs of DJD and as being most

commonly affected by this condition.14, 15

When we performed the study of evaluation of

radiographic signs indicative of DJD in cats and its association with macroscopic appearance of

articular cartilage,35

it became apparent that cartilage damage in this joint was located in the

medial compartment, specifically in the articular surface of the medial coronoid process and

medial aspect of the humeral condyle. Medial compartment elbow joint disease is recognized in

dogs49, 50

and is associated with medial coronoid process disease, humeroulnar incongruency and

abnormal forces acting in the medial compartment of the joint,51-53

but the cause of cartilage

damage in the medial compartment of the elbow joints in cats was unknown. Further evaluation

of the histopathological characteristics of the articular cartilage and synovium of the elbow joints

in cats54

did not reveal any of the features that are reported in dogs with fragmented coronoid

process (microcracks in the subchondral bone, increased porosity and loss of osteocytes).55, 56

We

did not perform histomorphometry to evaluate bone or osteocyte density, however these changes

were only seen in the areas of microcracks of the subchondral bone in dogs, and microcracks

were not present in our specimens. It is possible that fissures may have been missed during

processing of the samples for histopathological evaluation. Nevertheless, since no evidence of

fragmented medial coronoid process or a histologic reaction to an adjacent microfracture was

present in any of the specimens and fissuring or fracture of the coronoid process was not seen

during macroscopic evaluation of any of the joints, we concluded that fragmentation of the

coronoid process is not part of the pathogenesis of feline elbow DJD in the cases we evaluated.

Some of the changes observed in the subchondral bone in the samples evaluated in our study

were similar to those described in the subchondral bone of the medial coronoid process from

104

dogs with fragmented medial coronoid process (cartilage islands and fibrosis of the bone marrow

spaces)56

, but these lesions are nonspecific responses of bone to a variety of insults and are not

unique to coronoid disease. The cartilage islands within the subchondral bone observed in our

specimens were likely consequence of the degree of cartilage degradation rather than pathology

originating in the subchondral bone that leads to medial coronoid fragmentation.

The cause of elbow DJD in cats with this pattern of medial compartmentalization is still

unknown. One of the theories proposed for the pathogenesis of fragmented coronoid process in

dogs is the presence of abnormal loading forces in the elbow joint resulting from asymmetric

growth of the radius and the ulna which causes increase loads in the coronoid process and

subsequent fragmentation. Perhaps the same theory could explain why the lesions are

concentrated in the medial compartment of the elbow joints in cats. In this case, further

investigation will be necessary to elucidate why fragmentation of the medial coronoid process

does not happen as a result of these theoretical abnormal loadings in feline species.

Histopathological characteristics of the free intra-articular osteochondral fragments and

changes observed in the synovial stroma in the elbow joints seem to indicate that those fragments

originate from the synovial membrane and therefore are consistent with synovial

osteochondromatosis secondary to degenerative joint disease. Mention of feline synovial

chondromatosis in the literature is scarce and in some cases the intra-articular fragments were

referred to as “osteochondromas” although macroscopic and histopathological characteristics are

consistent with our findings.57, 58

Evaluation of the synovial membrane in the elbow joints from cats with and without DJD

revealed that severe synovial inflammation was not seen in any of the samples evaluated and

105

overall there was only mild inflammation in the synovium and very little synovial lining

hyperplasia even in those elbow joints in which the articular cartilage was ulcerated. This

suggests that the elbow lesions in our cases were not primary inflammatory in origin. Low

synovitis scores have also been reported in dogs with different degrees of cartilage fibrillation

secondary to fragmented coronoid process56

, and these results are consistent with Krenn et al.59

where the mean synovitis score of human patients diagnosed with osteoarthritis was only 2

(range 0-6). It was not surprising to not see ulceration of the epithelial lining of the synovial

membrane or severe inflammatory infiltrate of the synovial stroma since these features seem to

correspond only with reactive or rheumatoid arthritis. It was not known if the animals included in

our study were painful to manipulation of those joints, but if those joints were painful, the source

of pain may be coming from a source other than the synovial membrane, since synovitis does not

seem to be a consistent feature in feline elbow DJD.

We believe our studies have contributed to improve the understanding of the radiological

and histopathological characteristics of feline appendicular degenerative joint disease. Important

and common radiological features found in feline joints such as meniscal mineralization have

been found to correlate with severe cartilage damage in some cases and very well known causes

of elbow DJD in dogs that were mentioned as possible causes of feline elbow DJD have been

ruled out to be present in these species. Many questions still remain without answer and further

studies are necessary to elucidate more aspects of the etiology and clinical significance of this

disease in domestic cats.

107

CONCLUSIONS

109

1. Ninety-one percent of domestic cats have at least 1 appendicular joint with radiographic

signs of DJD and fifty-five percent of domesticated cats have radiographic signs of DJD in

the axial skeleton. Overall, 92% of domestic cats have radiographic evidence of DJD

somewhere in the skeleton.

2. The appendicular joints and spinal segment most frequently affected by radiographic signs

of DJD are the hip, followed by the stifle, tarsus and elbow joints, and the thoracic segment

respectively.

3. The appendicular joint with the most severe radiographic signs of DJD is the elbow joint

and the spinal segment with the most severe radiographic signs of DJD is the lumbosacral

region.

4. There is no evidence of association between DJD scores and the variables sex, percent of

time spent indoors/outdoors, vaccination status (rabies, FeLV, FVRCP), use of flea/tick

preventatives and FeLV or FIV status. However there is overwhelming evidence that the

total DJD radiographic score changes with the age of the cat.

5. Digital radiographs are equally or more sensitive for detection of articular degenerative

changes when compared with analog radiographs.

6. The most common radiographic features indicative of DJD are joint-associated

mineralizations for the elbow joint, tarso-metatarsal dorsal bone proliferation in the tarsal

110

joint, intra-articular mineralizations in the stifle joint and osteophytes in the coxofemoral

joint.

7. The joint most likely to have cartilage damage without radiographic evidence of DJD is the

stifle followed by the coxofemoral joint, elbow and tarsal joint.

8. The digital radiographic finding indicative of DJD with the greatest association with

cartilage damage is the presence of osteophytes for the elbow, tarsal and coxofemoral joints,

and intra-articular mineralizations for the stifle joint.

9. Forty-six percent of domesticated cats have radiographic signs consistent with meniscal

mineralization in one or both stifle joints.

10. Meniscal mineralization in domestic cats is bilaterally symmetrical, located in the cranial

horn of the medial meniscus and can present as a single area or multiple areas of

mineralizations.

11. The severity of the radiographic signs indicative of DJD and severity of macroscopic

cartilage damage in the stifle joints of domestic cats are significantly higher for stifles with

meniscal mineralization compared with stifles without meniscal mineralization.

111

12. Presence of meniscal mineralization in domesticated cats is associated with medial

compartment joint disease of the stifle joint as indicated by the presence of cartilage damage

on the medial femoral condyle and medial tibial condyle.

13. The appendicular joint with the greatest extent of macroscopic cartilage damage is the elbow

joint. This joint is followed by the stifle, coxofemoral and tarsal joints.

14. Macroscopic and histological evaluation of the articular cartilage of the elbow joint in

domesticated cats indicates the presence of medial compartment joint disease for which a

cause has not been identified.

15. Feline elbow joints evaluated with radiographic signs of DJD, articular cartilage damage

and intra-articular osteochondral fragments do not have macroscopic or histological

evidence of presence of fragmented medial coronoid process.

16. The presence of intra-articular osteochondral fragments in the elbow joints of domestic cats

is consistent with synovial osteochondromatosis secondary to degenerative joint disease.

113

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